Bioinspired and biointegrated materials as new frontiers nanomaterials VII

Resume : After three years of exile in Lille because of the renovation and extension of the Congress Center we are happy to be back home in Strasbourg and even more because we have an exceptional local speaker : Jean Pierre Sauvage a Nobel Laureate in Chemistry from Strasbourg. The University of Strasbourg is by far not the largest with >50,000 students but it can claim the surprising number of 4 Nobel laureates. Strasbourg is a really open international city, and the high level of E-MRS conferences can be judged by them being honoured by having had around 15 Nobel Laureates as speakers Jean Pierre SAUVAGE started his research activities here under the leadership of J.M. LEHN, the 1987 Nobel in Chemistry in 1971and joined CNRS in the same year. He spent 1973-74 in Oxford and was nominated as Research Director at CNRS in 1979 where he was awarded the Silver Medal of CNRS in 1988. RESEARCH BREAKTHROUGHS Even though it was predicted by Richard Feynman that nano machines will be developed as early as 1950, the first significative steps towards a molecular machine were achieved only around 1983 when J.P. Sauvage invented a CHEMICAL METHODOLOGY combining two molecules linked by strong covalence bonds, in which the atoms share the electrons incommon. These two molecules have to be interlaced and mobile one with respect to the other. Sauvage was able to develop a reproducible technique with a decade better efficiency the those previously found. I remember in an interview in the French Journal, La Recherche, he said around 10 years ago that everything is still very fundamental and that there is a long way to go . But, some researchers are quite innovative and 2000 saw the first engine! In newspapers reports in 2016 the structure of such a molecular “muscle”, a series of pictures were published with 3 antic symboles, going back to different philosophies here is my open question: Did the 3 Nobel Laureates discover something new, or was already everything known at that time? However, J.P. Sauvage will explain it to you in detail . Prof Sauvage we are highly honoured that you have found the time to be here today, despite the pressures that you are currently under and we are looking forward to hearing you now.

Resume : The area named "Chemical Topology" is mostly concerned with molecules whose molecular graph is non planar, i.e. which can not be represented in a plane without crossing points. The most important family of such compounds is that of catenanes. The simplest catenane, a [2]catenane, consists of two interlocking rings. Rotaxanes consist of rings threaded by acyclic fragments (axes). The simplest rotaxane, a [2]rotaxane, contains two non-covalently connected components : a ring and an axis, the axis being end-functionalised by bulky groups preventing unthreading of the non cyclic fragment from the cycle. Interlocking ring compounds have attracted much interest in the molecular sciences, first as pure synthetic challenges and, more recently, as components of functional materials. In recent years, spectacular progress has been made. Highly functional and complex systems have been reported by several research teams, demonstrating the power of modern synthetic tools based on "template effects". Separately, the field of artificial molecular machines has experienced a spectacular development, in relation to molecular devices at the nanometric level or mimics of biological motors. In biology, motor proteins are of the utmost importance in a large variety of processes essential to life (ATPase, a rotary motor, or the myosin-actin complex of striated muscles behaving as a linear motor responsible for contraction or elongation). A few recent examples are based on simple or more complex rotaxanes or catenanes molecular machines. Particularly significant examples include "molecular shuttles" as well as multi-rotaxanes reminiscent of muscles or able to act as switchable receptors. The molecules are set in motion using electrochemical, photonic or chemical signals. Examples will be given which cover the various approaches used for triggering the molecular motions implied in various synthetic molecular machine prototypes. Finally, potential applications of molecular machines will be discussed.

Resume : In this talk we will introduce the Rosette Nanotubes (RNTs) as a safe, tunable, and effective nanocarrier that can efficiently deliver a therapeutic RNA payload to a target cell. RNTs are biologically inspired nanomaterials created through the self-assembly of a DNA base analog (G/\C), exhibiting tunable chemical and physical properties. A defining characteristic and strength of the RNTs as a drug delivery vehicle is the ability to display various functional groups on their surface via self-assembly, conferring to them tunable physical (stability, dimensions), chemical (surface charge and channel properties), and biological (targeting peptides, bioactive molecules) properties. Such exquisite level of control allows to rationally design delivery systems that (a) evade the immune system, (b) encapsulate drugs, (c) actively or passively cross cellular membrane, (d) display bioactive drugs and exert a biological function, (e) display radioactive or photoactive probes to track and kill cancer cells, (f) escape the endosome when functionalized with positively charged amino acids and peptides, and (g) disassemble into innocuous small molecules after delivering their payload. Our multi-modal delivery system uses a multi-pronged approach to penetrate the target tissue and deliver therapeutic agents, all with one self-assembled biocompatible nanomaterial construct.

Resume : Supramolecularly engineered hybrid materials containing graphene are key multifunctional systems for applications in (opto)electronics and energy. The tuning of their dynamic physical and chemical properties can be achieved via tailored covalent or non-covalent interactions with ad-hoc macromolecules.[1] My lecture will review our recent findings on: (i) The harnessing of the yield of exfoliation of graphene in liquid media by mastering the supramolecular approach via the combination with suitably designed functional molecules possessing high affinity for the graphene surface, leading ultimately to the bottom-up formation of optically responsive graphene based nanocomposites for electronics. [2] (ii) The tuning of the graphene properties by combining them with organic semiconductors as a strategy to exploit the tunable ionization energy of thermally annealed liquid phase exfoliated graphene to modulate the transport regime as well as to fabricate new memory devices.[3] (iii) The bottom-up formation of graphene based 3D covalent frameworks with tunable intersheet distance, exhibiting large specific surface areas which determine extremely high performance in supercapacitors.[4] Our approaches provide a glimpse on the chemist?s toolbox to generate multifunctional graphene based nanocomposites with ad-hoc properties to address societal needs in electronics and energy applications. References: [1] (a) Chem. Soc. Rev. 2014, 43, 381?398 (b) Adv. Mater., 2016, 28, 6030?6051. [2] (a) Angew. Chem. Int. Ed. 2014, 53, 10355?10361 (b) Small 2015, 11, 1691-1702. (c) Nat. Commun. 2016, 7, 11090. (d) Nat. Commun. 2016, 7, 11118. [3] (a) Adv. Mater. 2014, 26, 4814-4819. (b) ACS Nano, 2015, 9, 2357?2367. [4] Small 2016, 12, 1044-1052.

Resume : Development of carbon-based materials to remove extracorporeally anti- and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-8, and IL-6 from the circulatory blood stream is a challengeIn direct hemoperfusion techniques, it is important that the carbon-based adsorbents do not cause blood coagulation, hemolysis, platelet destruction and release of microparticles [1]. Despite generally good biocompatibility and adsorption properties, some limitations of carbon include lack of pore size control. It has been shown that the control of pore size with a large volume of slit-shaped mesopores (specifically in carbide-derived carbons) is a key factor to achieving efficient removal of proteins [2,3]. So the question arises: How does one match the pore size to a specific molecular size of proteins? This cannot be done based only on the porous texture, such as a high surface area and a large volume of mesopores. Apparently, the properties that control this adsorption process include the charge of proteins, van der Waals interactions, and hydrophobic interactions between adsorbent-adsorbate, in addition to a large and accessible surface area. The effects of protein-surface interaction on protein adsorption are complex due to a large number of contributions to the overall interaction. To better understand the protein-surface interactions, we used expanded graphite and graphene nanoplatelets as prospective biomedical materials for hemoperfusion. 1. Y. Fuchigami, T. Nakashima. U.S. Patent 4,248,736; 1981. 2. S. Yachamanei, G. Yushin, S.H. Yeon, Y. Gogotsi, C. Howell, S. Sandeman, G. Phillips, S. Mikhalovsky. Biomaterials 2010, 31, 4789-4794. 3. V. Presser, S.-H. Yeon, C. Vakifahmetoglu, C. A. Howell, S. R. Sandeman, P. Colombo, S. Mikhalovsky, Y. Gogotsi. Adv. Healthcare Mater. 2012, 1, 796-800.

Resume : Diamond has ‘come of age’ as a material for technology and life science applications. Despite its reputation as a gemstone, high grade single crystal diamond can be grown in the laboratory at modest cost. Other forms of diamond, such as microcrystalline and nanocrystaline films can also be prepared, as can particulate nanodiamonds (typically ~5nm in size). Boron doping can mean that the normally highly electrical resistive material can be changed into both an n-type semiconductor and a quasi-metal. Diamond in its single crystal and polished polycrystalline forms has been shown to be ‘bio-inert’ when it comes to hippocampal neuronal cell attachment. For example, in a study some time ago, we showed that a patterned ECM protein tracks on diamond surfaces could be used to ‘steer’ the subsequent outgrowth of attached neurons into functioning, well defined, networks, given the inert nature of the diamond surface [1]. This position changes dramatically when nanostructured diamond is used, and most notably when surfaces are coated with nanodiamonds (NDs). In such a case we have shown that the NDs promoted adhesion of effective outgrowth without the purposeful addition of ECM proteins, and fully adherent functioning networks could be formed through this approach [3]. More recently, we have shown that nanostructured boron-doped diamond is suited to the attachment and proliferation of human neural stem cells, with no apparent toxic effects [4]. Diamond surfaces can also be chemically functionalized; we have shjpown that human neural stem cell differentiation can be influenced by this process [5]. This paper will briefly discuss the nature and properties of nanodiamonds, and then review the work performed at UCL on the interaction of nanodiamond films and nanodiamonds with neurons. 1. Ordered growth of neurons on diamond Specht CG, Williams OA, Jackman RB, Schoepfer R Biomaterials 26 (2005), 828-828 2. Thalhammer A., Edgington R.J., Cingolani L.A., Schoepfer R., Jackman,R.B. The use of nanodiamond monolayer coatings to promote the formation of functional neuronal networks Biomaterials 31, (2010) 2097-2104 3. Patterned neuronal networks using nanodiamonds and the effect of varying nanodiamond properties on neuronal adhesion and outgrowth Edgington R, Thalhammer A, Welch J, Bongrain A, Bergonzo P, Scorsone E, Schoepfer R and Jackman RB Journal of Neural Engineering, 10 (2013), 056022 4. Biocompatibility of nanostructured boron doped diamond for the attachment and proliferation of human neural stem cells Alice C. Taylor, Barbora Vagaska, Robert Edgington, Clément Hébert, Patrizia Ferretti, Philippe Bergonzo and Richard B. Jackman Journal of Neural Engineering, 12 (2015), 066016 5. Surface functionalisation of nanodiamonds for human neural stem cell adhesion and proliferation Alice C Taylor, Citlali Helenes González, Benjamin Miller, Robert J. Edgington, Patrizia Ferretti, Richard B Jackman Scientific Reports (Submitted).

Resume : In this talk I will introduce the problem of manipulating and controlling things on a nanometric scale. The self-assembly ability of molecules is of fundamental importance in modern science and technology, making possible to produce creative nanostructures with a precision that is not achievable with classical lithographic miniaturization techniques. The molecular self-assembly process is driven by different non-covalent and reversible interactions, which may be tailored in order modulate the final architectonic of the supramolecular structure obtained.[1] The most fascinating examples of supramolecular systems comes from Nature: by molecular organization, biological systems reached the level of sophistication which made possible to support life. One of the main components of biological systems are amino-acids, which are used as building blocks for the construction of proteins. A number of non-covalent interactions, among them the aggregation of helical segments into a more specific spatial conformation, drives the system into a specific three dimensional structure, which makes proteins the molecular motors par excellence. Imitating Nature, via helical peptide self-assembly on surface, it is possible to obtain films with tunable physical (patterning, molecular packing), chemical (surface charge and hydrophilicity properties), optoelectronic, biological (sensing) and biocompatible properties. Moreover, the macrodipole moment associated with the vector sum of the individual peptide dipoles in a helical secondary structure gives rise to an intrinsically polar SAM, which favours electron transfer in one precise direction and facilitates light-induced electron-hole separation, for appropriately placed chromophores [2]. I will talk in this presentation about the self-assembly properties of peptides on surface [3,4], on the modulation of their supramolecular structure by the proper design of the molecules and on their applications as artificial leaves[5,6]. References. 1. Lettieri R., Di Giorgio F., Colella A., Magnusson R., Bjorefors F., Placidi E., Palleschi A., Venanzi M., Gatto E. DPPTE Thiolipid Self-Assembled Monolayer: A Critical Assay. Langmuir 32, 11560–11572 (2016). 2. Yasutomi S., Morita T., Imanishi Y., Kimura S. A Molecular Photodiode System That Can Switch Photocurrent Direction. Science 204, 1944-1947 (2004). 3. Gatto E., Porchetta A., Scarselli M., De Crescenzi M., Formaggio F., Toniolo C. & Venanzi M. Playing with peptides: how to build a supramolecular Peptide nanostructure by exploiting helix···helix macrodipole interactions. Langmuir 28, 2817−2826 (2012). 4. Longo E., Wright K., Caruso M., Gatto E., Palleschi A., Scarselli M., De Crescenzi M., Crisma M, Formaggio F, Toniolo C. and Venanzi M. Peptide flatlandia: a new-concept peptide for positioning of electroactive probes in proximity to a metal surface. Nanoscale, 7, 15495-15506 (2015). 5. Gatto E., Quatela A., Caruso M., Tagliaferro R., De Zotti M., Formaggio F., Toniolo C., Di Carlo A., Venanzi M. Mimicking the Nature: A Novel Peptide-Based Bio-Inspired Approach for Solar Energy Conversion. ChemPhysChem 15, 64-68 (2014). 6. Venanzi M., Gatto E., Caruso M., Porchetta A., Formaggio F., Toniolo C. Photoinduced Electron Transfer through Peptide-Based Self-Assembled Monolayers Chemisorbed on Gold Electrodes: Directing the Flow-in and Flow-out of Electrons through Peptide Helices. J. Phys. Chem. A, 118, 6674-6684 (2014).

Resume : Nanoscale optical labeling is an advanced bioimaging tool. There is a variety of fluorescence biolabels such as organic molecular dyes, genetically encoded fluorescent proteins, semiconductor quantum dots and metal gold-based nanostructures. In this work we focus on the development of a novel class of visible peptide nanodots for advanced, biocompatible imaging applications. Bioorganic nanodots of different origin, self-assembled from chemically synthesized peptide biomolecules of different origin, were observed in our works. We propose two different methods to create fluorescent peptide nanodots. The first method is a chemical modification method of bionanodots based on organic dyes molecules conjugated to biomolecules. The second method is based on a thermostructural process in these bionanodots that leads to formation of -sheet secondary structure. As we recently discovered, ultrashort dipeptide nanoensembles, which are rich in ordered -sheets, demonstrate blue/green fluorescence. The visible photon emission is ascribed to reconstruction of hydrogen binding bonds due to protons transfer between the N- and C-termini of adjacent fibril strands of -sheet structure. This process results in low energy electronic transitions and fluorescence in the visible region. The authors appreciate support of Ministry of Science, Technology & Space of Israel.

Resume : Through the development of miniaturized biodevices involving groundbreaking nanotechnologies, the common dreams of many years regarding miniaturized implanted devices are soon to become a glad reality. In fact, these devices are getting more reliable and efficient, even if some important topics remain partly unexplored. Among them, remote communication with implanted devices is still an open subject. The transformative applications of implanted micro and nanotechnology involve not just single biodevices working independently, but groups of them working in a network. Thus, before the promise of implanted nanotechnology can be fully achieved, the problem that remains to be solved is communication among nanodevices. Nature faced and solved these problems by means of a strategy that rely on the release through the biological fluids of molecules acting as “chemical messengers”. Even if the biological communication networks are still too complex to be replicated, in all our views, bio-inspired molecular communication represents definitively a very promising strategy. In this work, we present a critical analysis on the problem of molecular communication through body fluids focusing on the selection and synthesis of a capable molecular messenger. Starting from the theoretical model of advection and diffusion of chemical signals in confined pathway we propose a specific non-linear receiver’s response to the concentration. Accordingly, we synthesized a nanometric molecular messenger based on carboxylic quantum dots. A lab-scale prototypal molecular communication system is presented as a platform that could be used to evaluate chemical signals transfer in body fluids as an alternative to electromagnetic communication.

Resume : Aptamers are synthetic nucleic acids that could selectively bind to their target molecules similiar to the antibodies [1-4]. The SELEX (Systematic Evolution of Ligands by Exponential enrichment) method has been used for the synthesis and the selection of aptamers to their specific target molecules. The improved stability properties including resistant to denaturation and degradation, easy modification, target adaptability and easy-to-stock make them more advantageous comparison to antibodies and ideal candidates as protein recognition elements in a wide range of bioassays, and also for diagnostic applications, especially aptamer based biosensors "aptasensors" [3-8]. An overview to the representative studies of nanomaterials based electrochemical aptasensors has been presented herein with their advantages and further applications. References 1- J. Muller, B. Isermann, C. Ducker, M. Salehi, M. Meyer, M. Friedrich, T. Madhusudhan, J. Oldenburg, G. Mayer, B. Potzsch, Chem. Biol. (2009) 16, 442-451. 2- M. Mascini, I. Palchetti, S. Tombelli, Angew. Chem. Int. Ed. (2012) 51, 1316-1332. 3- A. Erdem, H. Karadeniz, G. Mayer, M. Famulok, A. Caliskan, Electroanalysis (2009) 21, 1278-1284. 4- E. Eksin, G. Congur, A. Erdem, Aptasensor Technologies Developed for Detection of Toxins, In: Ed. D.P. Nikolelis, G-P. Nikoleli (eds.) Biosensors for Security and Bioterrorism Applications (2016) pp. 249-259, Springer, Ottawa, ON, Canada. 5- F. Rohrbach, H. Karadeniz, A. Erdem, M. Famulok, G. Mayer, Analytical Biochemistry (2012) 421, 454-459. 6- A. Erdem, G. Congur, Sensors and Actuators B: Chem. (2014) 196, 168-174 7- A. Erdem, G. Congur, Talanta (2014) 128, 428-433. 8- A. Erdem, E. Eksin, M. Muti, Colloid. Surf. B: Chem. (2014) 115, 205-211. Acknowledgements. A.E acknowledges as the Project Investigator for the financial support from Turkish Scientific and Technological Research Council (TUBITAK) (Project no.111T073), and she also would like to express her gratitudes to the Turkish Academy of Sciences (TUBA) as the Principal member for its partial support.

Resume : The color of various butterflies may originate not only from pigments, but from photonic nanoarchitectures found in the scales covering their body and wings, too [1]. The optical spectrum of these scales – usually of blue and green color – shows reversible changes [2] when the sample of the wing is exposed to an air–volatile vapor mixture. As we have shown earlier, these changes are chemically selective and depend monotonously on the vapor concentration. As the color change of the photonic nanoarchitecture is based on a capillary condensation process [3], it also depends on the temperature. Vapors influence the optical spectrum by several possible mechanisms, as liquid condensation in the air voids inside the photonic nanostructure and swelling of the chitin walls themselves. We performed full 3D electrodynamic calculations and compared the simulated spectra to the measured ones in order to reveal the influence of these possible processes on the optical response. [1] L. P. Biró & J. P. Vigneron, Laser Photonics Rev. 5, 27–51 (2011). [2] G. Piszter et al., Opt. Expr. 22, 22649 (2014). [3] K. Kertesz et al., Mat. Sci. Eng. C 39 221–226 (2014).

Resume : The synergetics of the four branches of modern science and technology: nanotechnology, biotechnology and biomedicine, information technology and high-performance computer systems, and cognition science as an interdisciplinary convergence of psychology, linguistics, anthropology, neuroscience and artificial intelligence computer technology, called after NBIC (nano-bio-info-cogno) requires the creation and development of new approaches and modern technology to modeling and synthesis of cyber-physical and bio-cybernetic systems. The aim of this work was to study the basic bio-inspiring principles of modeling and design of this self-organized bio-robots, cyber-systems and of models with feedback for functional adaptability cyber-systems to resolving tasks. As a result, studies have shown that under conditions of partial uncertainty of input data the functional resistance have systems with self-reconfigurable architecture. The reconfigurability of cyber-systems should be considered separately for the physical / biological and informational levels. The use of artificial intelligence technology enables make deep analysis of information but is not sufficient to fully adapt the system to the external environment. A prerequisite here is technical (technological) capacity of the system to the correction of its own architecture. The functionality of the information management algorithms for input and control of data and the sensitivity of measuring part transducers of physical quantities in the system feedback determined by parameters of the sensors. It is clear that bio-inspired and bio-integrated microrobots, which are uses such sensors, including semiconductor, is nano- and micro-structured. However, the use of bio-inspired principles of structural organization of cyber systems appropriate are correct as in nano / micro and mega scale. In this study also shows the examples of the full cycle of synthesis of cyber-systems from create intelligent sensors and measuring transducers information signals based on nanostructured semiconductors to functionally completed cyber systems for medical and environmental problems and technological profile.

Resume : We suggest and explore a novel route towards organic photodetectors sensitive to the circular polarization state of light. For this, we insert fullerene-blended thin films of homochiral squaraine compounds acting as highly circular dichroic active layer into conventional bulk hetero-junction photodiodes. The substitution pattern of non-toxic and environmentally stable dihydroxy-anilino squaraines is modified with a chiral pool reactant. The L-proline derivatives of choice are available in their enantiomerically pure forms making costly separation of racemic product mixtures obsolete [1]. Strong excitonic circular dichroism is measured in spin-casted neat and fullerene-blended thin films proving homo-chiral aggregation. The device performance depends on the blend ratio of squaraine and fullerene as well as on active layer thickness. In all cases, the devices suffer from a low fill factor, which is accompanied by a voltage-dependent photocurrent. The strong circular dichroism of the photoactive layer can enable a photocurrent-readout sensitive to the circular polarization state of the incident light [2]. Most promising devices in that sense contain a thick and donor-rich active layer with a spectral overlap of strongest photocurrent response and maximum circular dichroism within the green spectral range [3]. [1] R. S. Stoll, N. Severin, J. P. Rabe, S. Hecht, Adv. Mater. 2006, 18: 1271. [2] J. Gilot, R. Abbel, G. Lakhwani, E. W. Meijer, A. P. H. J. Schenning, S. C. J. Meskers, Adv. Mater. 2009, 22: 131. [3] M. Schulz, M. Mack, O. Kolloge, A. Lützen, M. Schiek, Phys. Chem. Chem. Phys. submitted 2017.

Resume : The self-assembly ability of molecules is of fundamental importance in modern science and technology, making possible to produce creative nanostructures with a precision that is not achievable with classical lithographic miniaturization techniques. In particular, self-assembled monolayers (SAMs) formed by helical oligopeptides are very promising materials, used as archetypal systems in various field of current nanoscience research, materials science, molecular biology and surface science, and with potential application as molecular sensors, optoelectronic and photovoltaic devices.[1-4] The motivation of using helical peptides for the creation of stable monolayers is to exploit the unique features of polypeptide molecules: they can be easily functionalized with smart groups, making possible to design the peptide sequence in a suitable way for their application; if functionalized with groups able to bind surfaces, they can form stable bio-hybrid monolayers with polar properties. The polarity is conferred by the macrodipole moment associated with the vector sum of the individual peptide dipoles in an alpha-helical secondary structure and it would favours electron transfer in one precise direction for appropriately placed chromophores, making the peptide to behave like a molecular diode. [5-7] In this work the photocurrent generation properties of mono- and bi-component peptide-based SAMs are studied by electrochemical and spectroscopic techniques. We discovered that the incident photon to current conversion efficiencies are correlated to the tridimensional peptide assembly capabilities, which are influenced by kinetic and thermodynamic factors. The importance of molecular organization for the optimization of the photoconversion efficiency will be emphasized. REFERENCES. [1] Gatto E., Stella L., Baldini C., Venanzi M., Toniolo C., Formaggio F. Superlattices Microstruct. 46, 34−39 (2009). [2] Gatto E., Porchetta A., Scarselli M., De Crescenzi M., Formaggio F., Toniolo C. & Venanzi M. Langmuir 28, 2817−2826 (2012). [3] Gatto E., Quatela A., Caruso M., Tagliaferro R., De Zotti M., Formaggio F., Toniolo C., Di Carlo A., Venanzi M. ChemPhysChem 15, 64-68 (2014). [4] Gatto E., Venanzi M. Israel Journal of Chemistry, 55, 671-681 (2015). [5] Gatto E, Caruso M., Porchetta A., Formaggio F., Toniolo C., Crisma M., Venanzi M. J. Pept. Sci. 17, 124–131 (2011). [6] Venanzi M., Gatto E., Caruso M., Porchetta A., Formaggio F., Toniolo C. J. Phys. Chem. A, 118, 6674-6684 (2014). [7] Gatto E., Caruso M. and Venanzi M. Handbook of Nanoelectrochemistry: Electrochemical Synthesis Methods, Properties, and Characterization Techniques, Aliofkhazraei, M., Makhlouf, A.S.H. eds, Pages 503-560 (2016).

Resume : The objective of must bioactive agents is to reach the inside of cells in order to perform an action leading to a biological benign response. Additionally, in genetic therapy, the introduction of molecules into the nucleus of a cell is needed. Cellular membranes offers a barrier to foreign molecules, that bioactive agents need to overcome. Skin is the first anatomical barrier to all kinds of pathogens, and the dermal administration of drugs has to overcome the very efficient protection it offers. We unfold an alternative method to transiently breach skin and cell membranes: the use of photoacoustic waves to open channels through those barriers, so that molecules can diffuse rapidly before they reversible close, within few minutes.[1,2] We describe the development of materials capable of the fast and efficient conversion of the energy in a laser pulse into a high frequency broadband pressure transient. This development was guided by the fundamental theoretical understanding of the processes involved, by the ability to develop adequate chromophores and substrates for light-to-pressure transduction, and by the understanding of the interaction between the photoacoustic waves and the biological membrane. Photoacoustic pressure waves generated by pico and nanoseconds laser pulses are shown to promote the dermal delivery of molecules as lidocaine, porphyrins, hyaluronic acid, and proteins, as well as cell transfection, with a reversibility that allows skin to recover its protective function and cells to remain viable. [1] G. F. F. Sá, C. Serpa, L. G. Arnaut, patent application WO/2012/144916, 19 April 2012. [2] G. F. F. Sá, C. Serpa, L. G. Arnaut, J. Control. Release, 167, 290-300 (2013). Acknowledgements: This work was performed under project “Photoacoustic Permeabilization of Biological Barriers – A Window for Drug Delivery and Gene Transfection” , with reference PTDC/QEQ-MED/3521/2014 funded by European Regional Development Fund (ERDF), through COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (OPCI), and by national funds, through FCT - Fundação para a Ciência e a Tecnologia I.P.”.

Resume : In mid of 1990s, the Light-Emitting Electrochemical Cells (LECs) came out as an alternative device concept to OLEDs[1]. The simple device architecture with a single organic layer and silver (Ag) cathode makes it advantageous for printing processes[2]. Today, one of the important arguments in the organic electronics field is to replace the synthetic polymers with biopolymers for biodegradable, biocompatible electronics[3-4]. This is comforted by the present scientific policy related to the humanity problem of creation of sustainability and minimizing the environmental pollution by reducing the electronic-waste[5]. In this work, DNA and the DNA-lipid complex (DNA-CTMA) were tested as Solid Polymer Electrolytes (SPEs) from aqueous and organic solvent media. Different salts were engaged as additional ionic source and the ionic conductivity for different ratios was investigated. The blend of SPEs and commercially available water-soluble blue emitter or organo-soluble yellow emitter was deposited between two electrodes to form the active layer. The luminance-voltage-current density characteristics and lifetime were investigated. The maximum luminance was recorded 2000 cd/m2 and 7 cd/m2 for yellow and blue BioLECs, respectively, with the turn on voltages of 3.5-10 V. The ionic conductivity of SPEs was obtained at the range of 10-6 S/cm at RT using impedance spectroscopy. Additionally, morphology of the blend films and electrochemical stability window of SPEs were explored. References [1] Q. B. Pei, G. Yu, C. Zhang, Y. Yang, A. J. Heeger, Science 269, 1086-1088 (1995). [2] G. Hernandez?Sosa, S. Tekoglu, S. Stolz, R. Eckstein, C. Teusch, J. Trapp, U. Lemmer, M. Hamburger, N. Mechau, Adv. Mat. 26, 3235-3240 (2014). [3] B. Singh and N. S. Sariciftci, Proc. OEC 1-4, (2006). [4] M. Irimia-Vladu, Chem. Soc. Rev. 43, 588-610 (2014). [5] I. Rau, J. G. Grote, F. Kajzar and A. Pawlicka, C. R. Physique 13, 853-864 (2012).

Resume : The world of the 21st century depends crucially on electronic devices that, in turn, rely on charge transport: transistors and chips have changed our life in a remarkable way... And this will continue. In Nature, electron transfer processes are of the utmost importance and wonderfully performed: just think of enzymes or the photosynthesis. Therefore, the development of electronic devices based on bio-molecules is highly desirable, also to give them a biocompatible essence. However, biomolecules have often little stability outside their natural environment. Our "bionic peptides" are biopolymers that possess - even when short - well-defined helical structures, remarkably stable under extreme environmental conditions. Their exciting features stem from their constituents: sterically hindered, non-coded α-amino acids. In this presentation, we will show our results towards the exploitation of the emerging properties of our bionic peptides to develop bio-molecular wires. We applied an exciting, bio-inspired approach based on nucleobase paring to give our peptides the skill to self-organize into long and tunable wires, thus propagating their effects in a domino-like fashion. The peptide fibers anchored on a gold surface were able to mediate the photocurrent generated by means of a porphyrin-based dye.

Resume : Recently, thin films based on an anilino-squaraine dye, blended with a commercial fullerene, have attracted quite some interest as possible artificial photoreceptors for vision restoration [1]. Upon thermal annealing these films become highly textured which enhances growth and adhesion of biological cells. To get more insight into the basic properties of thin squaraine films, we investigate the neat dihydroxy anilino squaraine 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl]-squaraine (SQIB), spin-casted on glass. Depending on the annealing temperature, SQIB crystallizes into two polymorphic structures: a monoclinic phase and an orthorhombic phase. They exhibit different absorption spectra with characteristic spectral signatures of molecular excitons with oblique transition dipole alignment and large Davydov splitting. Polarization-resolved confocal spectro-microscopy shows that the transitions of the excitonic states for each polymorph are polarized mutually perpendicular. The crystalline domains are distributed with random in-plane orientation on the samples, but X-ray diffraction reveals a strong out-of-plane orientation for both polymorphs. Their local in-plane orientation is deduced from spectro-microscopy recordings and polarized light microscopy. REFERENCES. [1] O. S. Abdullaeva, M. Schulz, F. Balzer, J. Parisi, A. Lützen, K. Dedek, M. Schiek, Langmuir 32, 9297-9302 (2016).

Resume : Hydrogen peroxide (H2O2) is an abundant molecule associated with several biological implications and reacts with natural enzymes such as catalase. Thus, H2O2 quantification in vitro constitutes a powerful tool for the detection of numerous disease biomarkers linked to enzyme-based assays. However, the label-free optical H2O2 biosensing in biological media and at low concentrations (sub-uM) has yet to be achieved. Herein, we rationally design a biomimetic artificial enzyme based on antioxidant CeO2 nanoparticles that become luminescent upon their Eu3+ doping. We vary systematically their size from 4 to 16 nm and study the size-effect on their catalase-mimetic activity manifested as the catalytic H2O2 decomposition in aqueous solutions. The strong CeO2 nanoparticle surface area-dependent antioxidant activity reveals that this process is mainly a surface-related phenomenon. The interaction of H2O2 species with the nanoparticle surface influences drastically the luminescence of CeO2:Eu3+ that originates from the surface layer rendering them highly sensitive H2O2 biosensors down to 0.15 M (5.2 ppb) in biologically-relevant solutions. Our results demonstrate how nanoparticle structural characteristics can be engineered to develop a highly sensitive H2O2 biosensor and link two, so far, unrelated research domains of the CeO2 nanoparticle antioxidant activity and luminescence based on their rare-earth doping. The here developed biomimetic artificial enzyme can become the starting point of sophisticated in vitro assays towards the highly sensitive detection of disease biomarkers.

Resume : Gas clathrate hydrates are crystalline inclusion compounds comprised of a three-dimensional network of hydrogen-bonded water molecules that can trap small gas molecules in the water cavities [1]. The interfacial interactions of clathrate hydrate containing systems are critical to the exploration of new frontiers of clathrate hydrate research, including advanced strategies in energy transportation and recovery, as well as overcoming the current barrier to energy storage of fuels in gas hydrate crystals [2,3]. The inter-particle interactions of clathrate hydrate crystals in water and oil continuous systems are examined at high pressure and low temperature conditions. Addition of surface-active molecules can be used to modify these processes, e.g. altering the crystal growth processes, or reducing the inter-particle interactions. The clathrate hydrate formation synthesis pathways can be a key strategy to designing higher storage capacity materials, and/or stabilizing new stable and metastable crystal structures. Structure metastability has been observed through spectroscopic and computational studies [4]. An overview of the key technological advancements and challenges in clathrate hydrate research, and the potential role of interfacial phenomena is presented. Acknowledgements: Funding and support is acknowledged from the CSM Hydrate Center Consortium, CSM REMRSEC, and the William K. Coors Fund and Coors Foundation. [1] E.D. Sloan & C.A. Koh, Clathrate Hydrates of Natural Gases, 3rd Ed., CRC Press, Boca Raton, FL (2007). [2] Z. Aman & C.A. Koh, Chemical Society Reviews, 45, 1678-1690 (2016). [3] L.J. Florusse, C.J. Peters, J. Schoonman, K.C. Hester, C.A., Koh, S.F. Dec, K.N. Marsh, E.D. Sloan, Science, 306, 469-471 (2004). [4] M.R. Walsh, C.A. Koh, E.D. Sloan, A.K. Sum, D.T. Wu, Science, 326, 1095-1098 (2012).

Resume : Neural stem cells (NSCs) have great potential for inducing repair in damaged areas of the nervous system. NSCs have the ability to self-renew, but also are able to differentiate into neurons, oligodendrocytes and astrocytes, which are the main cells in the central nervous system (CNS). Understanding the differentiation into these cell lineages is critical for regenerative therapy treatment of diseases such as Parkinson’s and Alzheimer’s, as detailed knowledge of how these specific cells are affected by disease is vital(1) In order to utilise the potential of stem cells in the field of regenerative medicine, it is essential that we are able to isolate the cells from their natural setting, propagate the cells in culture, and introduce the cells to a foreign environment(2). Given the outstanding biocompatibility of nanodiamonds (NDs) towards neuronal cells(3), nanocrystalline diamond (NCD) towards hNSCs(4) and their excellent ability to promote neuronal cell adhesion and outgrowth, the proliferation and differentiation of human NSCs (hNSCs) and their relationship with functionalised ND coatings has been investigated. Firstly, the interaction of hNSCs with varying surface functionalised NDs is investigated; with Oxygen-terminated functionalised surfaces favouring the proliferation of hNSC, compared to those with a Hydrogen-terminated surface. Quantitative cell count data of the hNSCs has been determined on the varying functionalised NDs as well as glass and tissue culture polystyrene (TCPS), along with contact angle and protein adsorption investigations suggesting a hypothesis for this result. Secondly ND surfaces of different functionalisation (H/O) are shown to influence the differentiation and proliferation of hNSCs in varying ways. hNSCs fate has been investigated via inducing and spontaneously differentiating the cells on varying nanodiamond substrates. 1. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. Nature Publishing Group; 2006 Jun 29;441(7097):1094–6. 2. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006 Jun 29;441(7097):1075–9. 3. Thalhammer A, Edgington RJ, Cingolani LA, Schoepfer R, Jackman RB. The use of nanodiamond monolayer coatings to promote the formation of functional neuronal networks. Biomaterials. 2010 Mar;31(8):2097–104. 4. Taylor AC, Vagaska B, Edgington R, Hebert C, Ferretti P, Bergonzo P, et al. Biocompatibility of nanostructured boron doped diamond for the attachment and proliferation of human neural stem cells. J Neural Eng. IOP Publishing; 2015 Dec 1;12(6):066016.

Resume : Large research efforts are being applied to develop alternatives to the current practices in the field of animal studies. The aim is to give an answer to the drawbacks of the use of animals to test drugs and medical devices for human use, meeting the so-called 3Rs principals of reduction, refinement and replacement in this field.[1] One powerful way in this diretion is represented by in vitro models where specific organs or tissues are recreated, recapitulating the in vivo mechanical and chemical environments experienced by cells in our body. We aim to reproduce the in vivo environment and to endow our device with the possibility of both monitoring cells processes and actively addressing them (i.e. electrical stimulation). To this end the scaffold material plays a pivotal role. A tridimensional electroactive scaffold has been developed starting from the conductive conjugated polymer PEDOT:PSS. Organic bioelectronic devices represent a novel technology allowing for label-free, non -invasive monitoring of cells through an electronic readout, additionally providing real-time measurements. In addition to the obvious advantages of low cost processing, compatibility with large area applications, and tunability of properties through chemical synthesis, organic electronic materials transcend the current state of the art in transduction and stimulation of electrical activity in cells displaying the ability to conduct ions, thereby providing a lower impedance connection to cells.[2] The developed scaffolds were showed to allow cells proliferation and its monitoring via an electronic read out (scaffolds impedance). The achieved results pave the way for the successful development of 3D models of different tissues and organs (i.e. blood brain barrier, bone) where it will be possible not only to monitor cells state but also actively stimulate them. [1] https://www.nc3rs.org.uk/the-3rs, [2] Cui, X. et al. Biomaterials 24, 777 (2003).

Resume : Natural hard materials such as mollusk shell, tooth enamel and bone possess outstanding combinations of stiffness, strength and toughness, which outclass most engineering materials. These natural materials are composed of stiff and strong building blocks which are arranged in designed architectures and interact through weak interfaces. The stiffness and strength of the materials come from the blocks, while their toughness come from intricate interplays between the architecture of the materials and their weaker interfaces. Inspired by these materials, this study demonstrates how simple cutting/assembling of ceramic bocks can be used to develop topologically interlocked ceramic panels with combinations of stiffness, strength, and impact resistance. The fabrication process results in low porosity ceramic blocks with smooth surfaces which were then assembled manually to make architectured panels. The panels were tested in impact loading condition. Compared to plain ceramic panels, the architectured panels was 50 times more impact resistant (in energy terms), at the expense of only 50-60 % decrease in stiffness and strength. This material demonstrates how bioinspiration, weak interfaces and material architecture can be harnessed to expand the capabilities of materials towards new directions.

Resume : Essential oils (EOs) produced from plant extracts have gained wide attention in recent years owing to its multifunctional properties. EOs have low toxicity and degrade quickly in soil and water, rendering them with environmental friendly property. Among the EOs, clove oil has been studied extensively due to its antimicrobial effect against a wide range of bacteria strains. However, the volatility and chemical instability of clove oil has severely limited its potential uses. In this study, clove oil is encapsulated using both in-situ and interfacial polymerization to enhance its chemical stability and prevent premature leakage under harsh environment. The formation of double layer polyurethane/poly (urea-formaldehyde) (PU/PUF) shell was confirmed through the cross-sectional view which shows distinct porous PU and dense PUF layers. Several reaction parameters were studied to fabricate microcapsules with different release profiles. Moreover, the release profile of these microcapsules was found to fit the Baker-Lonsdale model which identifies diffusion as the release mechanism. Through the standard plate count method, these microcapsules containing clove oil was proven to exhibit antibacterial activity against V. Coralliilyticus, a temperature dependent global marine pathogen that can cause coral diseases and contribute to marine biofilm. These microcapsules containing clove oil have great potential to be an eco-friendly solution to replace existing toxic antifouling agent.

Resume : Antioxidant enzymes are widely used in biomedical treatments or in chemical manufacturing processes to convert reactive oxygen species (ROS) into oxygen and water. However, the operating conditions (pH, temperature, ionic strength, etc.) can affect the enzyme properties and their reusability is often limited. To increase their functional stability and recyclability, enzyme immobilization on nanoparticles is a promising approach. We have investigated antioxidant systems based on layered nanomaterials such as titania nanosheets (TNS) or layered double hydroxides (LDH). Immobilization of antioxidant enzymes or enzyme-like complexes on the nanomaterials occurred through electrostatic and hydrophobic interactions. As the nanomaterials possessed limited stability at low/moderate salt concentrations, they were functionalized with polyelectrolytes in order to increase the colloidal stability of the system and also to further protect the enzymes. Upon polyelectrolyte adsorption, charge neutralization (aggregating system) or overcharging (stable suspension) of the particles could be observed at appropriate doses. The fully coated nanomaterials resulted in stable suspensions where primary particles were observed. Finally, the catalytic activity of the immobilized and embedded enzymes were measured and compared to the native one.

Resume : Biodegradable polymer particulate systems, such as poly(d-lactic-co-glyocolic acid) (PLGA), are frequently used as vehicles for controlled release of bioactive molecules. However, these systems suffer from the inherent problem of acidification of the internal environment due to the acidic degradation products during the release period. This has been reported to perturb the configuration of encapsulated peptides. Additionally, unrealistically slow and incomplete release of bioactive molecules are also other shortcomings of this otherwise very capable delivery system. To mitigate these issues, hollow PLGA particles are fabricated through a novel one-step osmogen mediated oil-in-water emulsion solvent evaporation technique. These hollow particles are loaded with Glucagon-like peptide-1 (GLP-1), an incretin hormone, to evaluate the efficacy of the system over the solid particles as a delivery vehicle. While the solid particles are shown to be suffering from incomplete release of the peptide, the hollow particles are shown to be easily optimized to achieve various release profiles, including complete release, by simply adjusting the amount of osmogen in the formulation. Additionally, these hollow particles are also shown to be effective in maintaining the structural integrity and bioactivity of the encapsulated peptide, while degradation of the encapsulated peptide was observed in the solid particles during the release study.

Resume : Inorganic nanoparticles (NPs) have the potential to dynamically tune the properties of extracellular matrices. They can be used to modulate cell adhesion, migration or activity [1], and to monitor parameters remotely and with a high spatial resolution [2,3]. In this study, we are producing biofibrillar hybrid matrices from fibre-forming proteins such as lysozyme or collagen, and a range of inorganic materials including gold nanoparticles and quantum dots [4]. We present 3 approaches for obtaining such bioinorganic scaffolds: where the NPs produced separately are grafted onto the nanofibers, where they are formed on the scaffolds or together with the scaffolds. Each approach leads to specific material dimensions and shapes, phase distribution and mechanical and optical properties as demonstrated by AFM and spectroscopic data. At last the behaviour of living cells is investigated for the different types of matrices. [1] Zhu, M.; Baffou, G.; Meyerbröker, N.; Polleux, J. ACS Nano 2012, 6, 7227–7233. [2] Debruyne, D.; Deschaume, O.; Coutiño-Gonzalez, E.; Locquet, J.-P.; Hofkens, J.; Van Bael, M. J.; Bartic, C. Nanotechnology 2015, 26, 255703. [3] Liu, L.; Zhong, K.; Meng, L.; Van Hemelrijck, D.; Wang, L.; Glorieux, C. J. Appl. Phys. 2016, 119, 224902. [4] Deschaume, O.; De Roo, B.; Van Bael, M. J.; Locquet, J.-P.; Van Haesendonck, C.; Bartic, C. Chem. Mater. 2014, 26, 5383–5393.

Resume : Coatings with antimicrobial properties are garnering interest to prevent implant-associated infections. Recently we showed that poly(arginine)/hyaluronic acid (PAR/HA) multilayers built with PAR chains constituted of 30 arginine residues (PAR30) have strong antimicrobial properties through a contact killing mechanism. This property is due to ability of PAR30 chains, when associated with hyaluronic acid, to diffuse in the multilayer. Secondly, we investigate the effect of the nature of the polyanion on the antimicrobial behavior of (PAR30/polyanion) multilayers against bacteria. Four polysaccharides, one polypeptide and one synthetic polyelectrolyte are investigated. Surprisingly, only HA leads to films with antimicrobial character. We relate this property to the strong diffusion capacity of PAR30 chains in (PAR30/HA) multilayers compared to their diffusion ability in the other (PAR30/polyanion) films. Through isothermal microcalorimetry experiments we also demonstrate that interactions in solution of PAR30 chains with the different polyanions are characterized by a negative reaction enthalpy for all the investigated polyanions except for HA, where the enthalpy of reaction is positive. Moreover, the molecular weight of HA is not a key parameter of the diffusion abilliity of PAR chains or for the bioactivity of the film. These results constitute an important step towards the establishment of rules to design contact-killing antimicrobial polyelectrolyte multilayers.

Resume : Photosynthesis, the conversion of sunlight to chemical energy, holds huge promise for energy production and storage, in both biological systems and inorganic bio-inspired ones. In higher plants, the light-dependent reactions of photosynthesis occur in sites with nanoscale geometry and heterogeneous protein composition: the thylakoid membranes inside chloroplasts. In these sites, ray optics fails to adequately describe light absorption. We address the complexity of thylakoid membranes, in terms of structure and light-harvesting protein composition, with a rigorous nano-optical approach. Remarkably, we demonstrate that the thylakoid membranes provide additional photonic functionalities to photosynthesis. Thylakoid membranes are arranged in cylindrical stacks called grana, and in neighboring lamellae. The light-harvesting complexes I and II are preferentially concentrated in the lamellae and in the grana, respectively. We study the effects of grana shape, size and separation by full-wave electromagnetic solvers, and correlate them to protein distribution. Our results reveal that photonic resonances and interferences are accountable for a rational light management in chloroplasts. Providing description of complex bio-systems in a rigorous approach used for solid-state photonics, our study unveils original aspects of natural photosynthesis and sets novel directions for bio-inspired inorganic light conversion devices.

Resume : Hierarchically organized nanoscale structures act as building blocks in the formation of both natural and man-made biosystems. Supramolecular interactions are involved in the assembly of highly ordered structures which are ultimately responsible for shape, structure and function of such biosystems. Whereas the overall assessment of these systems role is obtained by macroscopic evaluations, their nanoscale characterization is fundamental to uncover important underlying molecular mechanisms governing their complex behavior. Here we show how advanced scanning probe microscopy techniques can be successfully employed to characterize self-assembled bio-nanostructures thanks to their ability to simultaneously correlate the morphology with local properties at the nanoscale. Conductive Atomic Force Microscopy (C-AFM) for example is used to probe electrical conduction within nanostructures obtained by the self-assembly of biomolecules with organic polymers. Conductive polymers are here used to coat proteins superstructures, such as amyloid fibers,[1, 2] or to be incorporate into model lipid membranes,[3] by exploiting non-covalent interactions. In this way, the conductive properties of conjugated organic polymer are combined with the high structural order of biomolecular nanotemplates, with the perspective to be exploited in a variety of functional components, or possibly integrated into biological systems. The nanoscale characterization of bio-nanostructures by advanced Scanning Probe Microscopy opens fascinating perspectives for accessing new properties and processes within biosystems in a non-destructive manner, possibly enabling new modes of observing biological processes. [1] A. Elfwing, F. G. Bäcklund, C. Musumeci, O. Inganäs and N. Solin, Decorated Protein Nanowires with conductive properties, J. Mater. Chem. C, 3, 6499, 2015. [2] F. Bäcklund, A. Elfwing, C. Musumeci, F. N. Ajjan, V. Babenko, W. Dzwolak, N. Solin, O. Inganäs, PEDOT-S coated protein fibril microhelices, submitted for publication. [3] P. Johansson, D. Jullesson, A. Elfwing, S. I Liin, C. Musumeci, E. Zeglio, F. Elinder, N. Solin, and O. Inganäs, Electronic polymers in lipid membranes, Sci. Rep. 5, 11242, 2015.

Resume : Single-molecule nucleic acid electronic sensing has the potential to be developed into rapid, sensitive, accurate and low-cost point-of-care biosensors. In single-molecule electronic sensing, analytes are driven through a nanopore via electrophoresis. The temporary blockage of the pore will register an ionic current fluctuation. The electrical signal (current amplitude change, duration of fluctuation, substructure) reflects the identity of the analyte. To achieve the detection of specific nucleic acid sequences, we propose a sensing strategy that involves the attachment of complementary single-stranded DNA (ssDNA) probes as overhangs on a long ssDNA carrier strand. Complementary target sequences will hybridise to the probes, transforming the overhangs from a compact coil (unhybridised ssDNA) to a stiff rod structure (dsDNA). Thus, a large secondary current drop can be detected when a hybridised probe on the DNA carrier strand translocates through the nanopore. Multi-analyte detection will be investigated by attaching different probes on the same carrier DNA (from bacteriophage M13). Specific hybridised probes can be identified by converting temporal signals to spatial positions. Our group has recently reported the use of custom-designed, low noise (high current resolution), high bandwidth (detect fast events) current amplifiers to enhance signal output. The custom-designed electronics will allow us detect and differentiate between hybridised and unhybridised overhangs.

Resume : Cell-based therapy is the transplantation of living cells for the treatment of diseases and injuries. Such therapy offers a promising solution for the treatment of various pathologies that conventional medicine cannot cure effectively, thus encouraging future medical breakthroughs. For instance, cancer-fighting T cells may be injected in the course of cancer immunotherapy, and stem cells may treat neurodegenerative diseases, heart disease, muscular dystrophy and diabetes. A major obstacle in the advancement and implementation of cell therapy is the challenge of no-invasively tracking transplanted cells in the body. In vivo cell tracking could elucidate essential knowledge regarding mechanisms underlying the success or failure of therapy. An optimal solution for the challenge of cell tracking does not yet exist hence the need for an accurate imaging technique. We developed a novel methodology for longitudinal and quantitative in vivo cell tracking, based on the combination of CT as an imaging modality and gold nanoparticles as labeling agents. We were able to show that uniting the superior visualization abilities of classical CT with state-of-the-art nanotechnology is the key for high-resolution cell tracking. In the future, this technology has the potential to be applied clinically and to serve as an early warning system for patients after cell transplantation.

Resume : The design concept to create the stimuli responsive photoactive at visible range carbon tubes nanostructures is based on constructed molecular models for the photoemission of semiconductor carbon nanotubes (CNT’s) functionalized by attached to the core and ends photoactive molecular complexes: metal (d - transition metal Cu) - organic (azole ligand) complex or by this complexe with coordinative bonded biomolecule (histidine). The tubes are the building blocks for nanostructures organization due to bonds between the metal ions and the ligands or the histidine molecules at different tubes. The architecture (SEM images) and the photoemission (PL spectroscopy) for nanostructures from these functionalized MWCNT in adsorbed layer at silicon substrate are characterized. The SEM images for this layer are interpreted using proposed molecular architectures models for building blocks connected through Cu2 with attached two ligands molecules at different tubes cores and these bonds are partially retain in the complexes with coordinative bonded histedine molecules that can decrease formation of these structures due to their adsorbing on tubes. These layers with namely one and both two types of nanostructures are characterized by photoemission wide bands, having different intensities and different three subbands in visible range

Resume : Silk fibroin is a good candidate to fabricate conductive biomaterial for bioelectrical applications because of its excellent mechanical property, biocompatibility and biodegradability. The modification by conductive polymer can endow silk fibroin with novel conductive functionality. Poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT) and its derivatives are very potential for the modification due to the high conductivity, biocompatibility, environmental stability and light transmittance. However, the hydrophobic PEDOT monomers have difficulties in absorbing and synthesizing on the surface of silk fibroin. In order to improve the efficiency of the polymerization, sodium dodecyl sulfate (SDS) was adopted as surfactant while ammonium persulfate (APS) was used as oxidant. Poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-OH) was polymerized and covalently deposited as a conducting layer on the surface of RSF film. The effects of the dosages of surfactant and oxidant, initial pH value and monomer concentration on the conductivity and morphology of the film were investigated. Results showed that SDS plays an important role to construct smooth conductive coating with several microns. The conductive RSF film shows a square resistance on the order of 105Ω or a conductivity on the order of 10-3 S/cm. This modification can be applied for RSF materials with various forms including fiber, film, foam, mats and 3D scaffolds. It is also possible to construct a microfluidic device with integrated conductive RSF channel for further applications of biosensor, tissue engineering and organic electronics.

Resume : Adipose- derived stem cells (ADSCs) are a novel type of mesenchymal stem cells (MSCs). MSCs are widely used for differentiation to tissues and cells such as bone and muscle. Up until recently, the most common type of MSCs for clinical application were Bone Marrow-derived MSCs (BM-MSCs). Although BM-MSCs and ADSCs are similar in nature, ADSCs possess the superior capability of being easier to harvest: In the case of BM-MSCs, the procedure is more invasive and requires penetration of the hipbone. On the other hand, ADSCs can be obtained in a safer way and larger amounts, by using subcutaneous fat tissue. This makes them far more applicable in cases where invasive surgery is not an option, such as on infants and young children. ADSCs can differentiate into a range of cell types, such as bone, chondrocytes and neurons. Due to their accessibility, ADSCs are a particularly attractive solution for the correction of congenital defects, such as craniofacial defects using autologous grafts. Autologous grafts are of great significance for tissue engineering and regenerative medicine, as they are mitigating the risk of rejection, because they are derived from the patients’ own body. In the past, the interaction between human Neural Stem Cells (hNSCs) and nanodiamonds (NDs) has been widely investigated by our team [1]. NDs possess great biocompatibility properties and they have been shown to interact particularly well with hNSCs. Early in vitro results have also shown significant compatibility with ADSCs. In proof-of-concept experiments, oxygen-terminated NDs have been shown to function as a more efficient environment for the proliferation and differentiation of ADSCs than other types of ND-based microenvironments, creating optimal conditions for the development of a range of tissues potentially both in-vitro and in-vivo. [1] Biocompatibility of nanostructured boron doped diamond for the attachment and proliferation of human neural stem cells Alice C. Taylor, Barbora Vagaska, Robert Edgington, Clément Hébert, Patrizia Ferretti, Philippe Bergonzo and Richard B. Jackman J. Neural Eng. 12 (2015) 066016

Resume : Live cells are the basic working units in the biological tissue, performing different functions as natures? microreactor. Assembly of sub-compartmentalized microreactors has become an important approach to mimic cells due to the structure similarity, ease of encapsulation of different subunits with multiple cargos, and the controllable activity initiation. With the aim to make artificial hepatocytes, we designed different sized microreactors with entrapped enzyme loaded liposomal subunits using droplet microfluidic or the layer-by-layer assembling technique. First, the synthetic partner particles or capsules were co-cultured with biological hepatocytes and successfully incorporated into the growing cell culture, forming bionic tissue with artificial and biological components. The surfaces of the particles or capsules coated with different polymers facilitated a beneficial biological response, i.e., the integration of the artificial and biological hepatocytes in a co-cultured tissue sheet as well as co-cultured cell tissue spheroids. The biological hepatocytes proliferation in the bionic tissue was assessed. Furthermore, detoxification, a key function of liver cells, was performed by loading the enzyme catalase, which can remove the cytotoxic compound hydrogen peroxide (H2O2), into the liposomal subunits of the artificial hepatocytes. The viability of hepatocytes in the bionic tissue was improved in the presence of active microreactors. These findings are a major step towards the beneficial combination of biological and synthetics entities with potential impact in regenerative medicine. Key words: cell mimicry, sub-compartmentalized microreactor, hepatocytes, detoxification, bionic tissue

Resume : One of the latest trends in the fields of tissue engineering as well as oncological research is the development of in vitro systems mimicking specific target tissues. In this way, models will be available that replicate the tridimensional structure and microenvironment experienced by cells in the target tissue more closely than the 2D systems employed so far. Interestingly, in addition to chemical and mechanical cues, certain tissues are known to be regulated by endogenous bioelectrical cues. One such tissue is the bone. Indeed, it has been demonstrated to exhibit piezoelectric properties in vivo, generating electrical potential upon mechanical deformation and responding to electrical stimulation. Electrical stimulation has been proven to sustain cell proliferation as well as to boost the expression of genes related to stem cells osteogenic differentiation. The device that will be developed will consist of 3D electroactive porous scaffolds allowing both electrical stimulation of stem cells and the analysis of the differentiation process towards bone-forming cells.

Resume : Nanomaterials with luminescence in the short-wave infrared (SWIR) region are of special interest for biological research and medical diagnostics because of favorable tissue transparency and low autofluorescence backgrounds in that region. Single-walled carbon nanotubes (SWCNTs) show well-known sharp SWIR spectral signatures and therefore have potential for noninvasive detection and imaging of cancer tumours, when linked to selective targeting agents such as antibodies. However, such applications face the challenge of sensitively detecting and localizing the source of SWIR emission from inside tissues. A new method, called spectral triangulation, is presented for three dimensional (3D) localization using sparse optical measurements made at the specimen surface. Structurally unsorted SWCNT samples emitting over a range of wavelengths are excited inside tissue phantoms by an LED matrix. The resulting SWIR emission is sampled at points on the surface by a scanning fibre optic probe leading to an InGaAs spectrometer or a spectrally filtered InGaAs avalanche photodiode detector. Because of water absorption, attenuation of the SWCNT fluorescence in tissues is strongly wavelength dependent. We therefore gauge the SWCNT?probe distance by analysing differential changes in the measured SWCNT emission spectra. SWCNT fluorescence can be clearly detected through at least 20 mm of tissue phantom, and the 3D locations of embedded SWCNT test samples are found with sub-millimeter accuracy at depths up to 10 mm. Our method can also distinguish and locate two embedded SWCNT sources at distinct positions.

Resume : Bioinspired nanostructures demonstrate fundamental physical properties such as piezoelectric, nonlinear optical, electrooptical and optical waveguiding effects [1, 2]. This work is focused on a new phenomenon of a deep modification of electron-optical properties resulting in visible fluorescence of peptide triphenylalanine (FFF) nanoensembles folded into a beta-sheet secondary structure. Found two wide spectral bands of optical absorption and photonic emission in blue and green regions are attributed to a strong reduction of the energy gap of intermolecular hydrogen bonds of antiparallel beta-sheet supramolecular structures. Found intrinsic visible fluorescence in FFF-nanostructures is also observed in biological nanostructures of a different complexity from simple ultrashort aromatic and aliphatic di- , tri-peptides to long, containing dozens peptides, neurodegenerative amyloidogenic proteins [3] that allows to consider it as an optical signature of a fundamental biological beta-sheet biomolecular organization. It can be used both in bio-nano-photonics and medical diagnostics of protein misfolding diseases. The authors appreciate support of Ministry of Science, Technology & Space of Israel. [1] A. Handelman, S. Lavrov, A. Kudryavtsev, A. Khatchatouriants, Y. Rosenberg, E. Mishina and G. Rosenman, Nonlinear Optical Bioinspired Peptide Nanostructures. Adv. Optical Mater 1; 875-884 (2013) [2] A. Handelman, B. Apter, T. Shostak and G. Rosenman, Peptide Optical waveguides. J. Pept. Sci. (2016) [3] V. N. Uversky and Y. L. Lyubchenko, Bio-nanoimaging: protein misfolding and aggregation. Elsevier, UK, 2014.

Resume : In many blindness-causing diseases, photoreceptors degenerate whereas second order and projecting neurons are largely unaffected. Thus, one promising avenue to restore vision in affected patients is to develop artificial photoreceptors for retinal prosthetic devices [1]. Artificial photoreceptors based on organic semiconductors emerged as promising alternative for inorganic materials due to increased biocompatibility and the feasibility of direct optical stimulation [2]. We follow an electrophysiological patch clamp approach to conduct fundamental mechanistic studies on a model system, which consists of murine neuroblastoma (N2A) cells grown on a textured small molecular organic semiconductor thin film under physiological conditions. We have chosen a custom-made anilino-squaraine dye, shortly named SQIB, blended with a commercial fullerene as active layer of the artificial photoreceptor. Patch clamp recordings showed, that photoexcitation of the system with short light pulses, stimulated fast capacitive transmembrane currents in the N2A cells [3]. The electrical coupling between the artificial photoreceptor and the neuronal cells was fast and direct, but still was only of passive nature. To increase the capacitive coupling, we deposit an additional dielectric coating such as silicon dioxide onto the active layer. We conduct a systematic investigation of the impact of the dielectric coating on transient photocurrents within the electrolyte and the consequential transmembrane currents. Additionally, we monitor the stability of the modified artificial photoreceptor in physiological environment under illuminated conditions by atomic force microscopy. [1] L. Bareket-Keren, Y. Hanein, Int. J. Nanomed. 2014, 9: 65. [2] D. Ghezzi, et al., Nat. Photon. 2013, 7: 400. [3] O. S. Abdullaeva, M. Schulz, F. Balzer, J. Parisi, A. Lützen, K. Dedek, M. Schiek, Langmuir 2016, 32: 8533.

Resume : Cellulose nanocrystals (CNCs), nanorods produced by acid hydrolysis of cellulosic sources, are emerging as a new class of functional biomaterial. CNCs present a broad range of uses, for example in composites, cosmetics, security paper and medical devices [1]. The fascinating ability of CNCs to self-organize into a cholesteric liquid crystal phase, with a helical arrangement of the nanorods, is attracting substantial interest across different research fields [2]. It is important from an applied point of view since this arrangement gives a photonic band gap to the final dried CNC films, but also from a fundamental soft matter physics perspective, as many details of the CNC liquid crystal formation are far from being understood. A critical problem from an analytical, and likely also from an applied perspective, is the high length polydispersity of as-produced CNC samples. In this study, we introduce a method for fractionating the CNC nanorods, utilizing the spontaneous phase separation between isotropic and liquid crystalline phases, allowing us to narrow down the length distribution. The aspect ratio (length/diameter) has a strong effect on the period of the cholesteric helix, affecting the iridescent colors appearing in dried CNC films. We believe that a reduced polydispersity will allow us to better control the color of the finally dispersed films, compared to the natural polydisperse samples that are now being used in the community. We present how this affects the self-assembly process, and consequently the color formation in such bio-derived structural films. [1] J.H. Park et al., ChemPhysChem, 15, 7, pp. 1477-1484 (2014) [2] Lagerwall, J. P. F. et al. Cellulose nanocrystal-based materials: from liquid crystal self-assembly and glass formation to multifunctional thin films. NPG Asia Mater. 6, e80 (2014).

Resume : In nature, layered composite materials such as nacre are self-assembled from proteins and inorganic building blocks. Synthetic layered composites mimic some of the properties of nacre, but they are mostly prepared through layer-by-layer deposition, a lengthy approach for bulk materials preparation. New and faster assembly routes may be developed by taking advantage of the liquid crystalline behavior of colloidal suspensions. We combine gibbsite platelets with filamentous viruses, used extensively in materials science [1] and soft matter Physics as models for plates and rods forming colloidal liquid crystals [2]. The behavior of rod/plate mixtures explored here has only been studied in very few cases. We first ensure that the interactions between the particles are purely entropic, by modifying gibbsite particles surface to avoid electrostatic assembly with viruses. Using differential dynamic microscopy and fluorescence microscopy we obtain the dynamics of both systems independently and show how it depends on the ordering of the system [3]. The morphology and mechanical properties of obtained films are studied at nanoscale by means of atomic force microscopy. We demonstrate different cases of virus/platelet organization on surfaces and in thin films. [1] Cao, B. et al. Acc. Chem. Res. 2016, 49, 1111–1120. [2] Kirchenbuechler, I. et al. Nat. Commun. 2014, 5, 5060. [3] Lewis, A. H. et al. Soft Matter 2014, 10, 7865–7873.

Resume : Magnetically-modified (nano)fibers produced by electrospinning attract high attention in various areas of medicine, biosciences and biotechnology. This study deals with the developing of polyvinyl pyrrolidone/chitosan (PVP/CS) crosslinked electrospun fibrous platforms and their further modification by employing a post-magnetization process (i.e. the chemical co-precipitation method) for introducing magnetic iron oxide nanoparticles (FexOy NPs) onto their surfaces. These materials were characterized in regards to their composition, morphology, and thermal properties by XRD, SEM, TEM and TGA. The resulting magnetic electrospun fibrous (nano)textile were further evaluated as magnetoactive substrates for the immobilization of microbial cells, enzymes and low-molecular-weight affinity ligands. Acknowledgements The research was supported by the projects LD14075 and LO1305 (Ministry of Education, Youth and Sports of the Czech Republic) and the University of Cyprus Grant “Post-doctoral Researchers” supporting Dr. I. Savva. We are also grateful to Dr Eugenia Vasile (University Politehnica of Bucharest) for the TEM measurements.

Resume : Membrane proteins contribute to a number of crucial roles such as transport, mechano-regulation or signal transduction. For this reason, engineered proteins interacting with the cell membrane are expected to offer novel added functionalities. However, current protein engineering strategies often take considerably long time and show difficult tunability, making this process difficult to scale up and hindering the use of high throughput approaches. However, it seems DNA nanotechnology could overcome this issue. Although the use of free DNA as vaccination method has been reported, there is little research concerning its interaction with lipid membranes. Nevertheless, recent studies suggest that lipid-decorated DNA structures can bind to and penetrate lipid bilayers. Hence, we will exploit the tunability of water-soluble DNA nanostructures to explore how their interaction with lipid membranes differs according to their shape and functionalization. By using a fluorescent readout, we expect to elucidate how we can tune the degree of binding and penetration of these constructs. If successful, our results could be extrapolated to protein engineering, enabling faster paces and allowing a high throughput approach. Furthermore, the use of DNA nanostructures for replicating membrane proteins could be assessed, potentially enabling the creation of novel therapies.

Resume : In this work, we present a systematic ab initio study on the structural, electronic and mechanical properties of Ti-xNb (x < 35at%) alloys. This necessity is originated from the currently used Ti-6Al-4V implants that consist of cytotoxic elements and exhibit higher Young’s modulus (E~112GPa) compared to a bone (E < 30GPa), resulting in bone atrophy and implant loosening. Our results predict a variety of phases (including ω, α’, α’’ and β) depending on the Nb concentration, in agreement with previous works. The α′ and ω are favorable for Ti-xNb (x ≤ 6.25%at), the β phase is stable at high Nb compositions (x ≥ 18.75at%) while the α″ phase may form in intermediate concentrations. The α′ and ω hexagonal phases become unstable at high Nb content due to the electronic band filling at the Fermi level (EF), while in the cubic β-Ti-25 at%Nb the depletion of the occupied electronic states at EF results in a stable β-TiNb structure. Our results exhibit the Eω > Eα′ > Εα″ > Εβ sequence, revealing the importance of the phases coexistence for the E reduction. The Young’s modulus surface revealed high anisotropic E values for all Ti-Nb phases, while the Eβ along the [100] direction exhibits an E under 30GPa suggesting the importance of a Ti-Nb single-crystal growth for the design of low rigidity alloys. These results could enlighten the electronic origin of the Ti-Nb phase stability and thus be used for the design of novel alloys suitable for biomedical applications.

Resume : Nanoparticles are being increasingly recognized due to their potential utility in various sectors including nanomedicine. Herein, we have demonstrated a new strategy to synthesize multifunctional GO-wrapped ZnO nanoparticles (GO-ZnO nanohybrid) for targeting photodynamic therapy (PDT) under visible light irradiation. Folic acid (FA), a targeting agent toward cancer cells, was conjugated onto graphene oxide (GO) via imide linkage. The nanohybrids have shown pronounced improvement in tumor targeting, which has been demonstrated by MTT and cellular uptake assay. Due to the high electrical conductivity of GO, the interaction between GO and ZnO, and the inhibition of aggregation, the hybrid of GO-FA and ZnO significantly enhances the photodynamic activity, mediated by reactive oxygen species (ROS) generation under visible light irradiation. The study presents a novel tumor targeting photosensitizer and a promising strategy in PDT for cancer treatment.

Resume : Based-on Silicon element widely distributed in mammalian tissues, bare laser-synthesized Si nanoparticles (Si-NPs) appear promising tools for biomedical tasks. Here, we employ ultra-short laser method in aqueous solution to elaborate extremely stable colloidal Si-NPs solutions. The nanoparticles appear spherical with low size distribution ranging from few nm to tens of nm. Structural analysis evidences that Si-NPs are composed of Si nanocrystals surrounding with thin layer of SiOx (1≤x≤2) and exhibiting a negative charge surface of -35 mV ± 0.10. Moreover, by monitoring the amount of dissolved oxygen into the synthesis medium, we report a dependence of the dissolution rate of NPs in aqueous environment on the presence of oxidation-induced defects in the core of Si-NPs. By examining the interaction of bare Si-NPs with human cells after 72 h of incubation at different concentrations, we report no adverse effects up to high concentrations (50 µg/mL) and a good internalization via classical endocytosis mechanism. In addition, intravenous administration of Si-NPs using small animal model reveal any toxicity confirmed by behavior of mice, histological analysis and other key biochemical parameters. These encouraging results open exciting perspectives to develop bare laser-synthesized Si NPs as promising platforms in nanomedicine.

Resume : Hydrogels have been extensively investigated for biomedical applications and tissue engineering. Their biocompatibility and resemblance with living tissues make them ideal materials to be applied in drug delivery, biosensing and as scaffolds for cell growth.[1-4] Notably, the possibility to introduce various functional groups into the polymeric network provides wide scope for tuning the hydrogel properties, obtaining smart biomaterials. Herein we report the synthesis and characterization of polyamidoamine-based hydrogels with equilibrium water content (EWC) up to 96%. The properties of the material were tuned by varying reaction conditions, such as pH and the relative concentrations of monomers, obtaining hydrogels with improved swelling properties. In vitro and ex vivo tests assessed their efficacy as adhesive sealants for gastrointestinal fistulas. Our injectable hydrogels could pave the way to endoscopic non-invasive procedures for fistula treatment. Further experiments are still in progress to optimize the properties of these scaffolds and to explore their biocompatibility.

Resume : Packaging materials that cover or protect products to prevent deformation or spoiling have received much attention in polymer science and engineering fields over the last several decades. The recent increase in environmental concerns has demanded replacing conventional petroleum-derived plastics with alternative packaging materials based on bio-resources. Thus, diverse biopolymers such as poly(lactic acid), poly(hydroxy acid), and polycaprolactone have been widely investigated as eco-friendly packaging materials. Silk, a natural biopolymer, has been utilized in textile and biotechnological applications because of its exceptional mechanical and bio-relative properties. In addition, silk can be easily formed into mechanically robust films with excellent surface qualities (surface roughness rms <5 nm), high transparency (>90% transmission in the visible range), and good chemical resistance properties. Thus, silk is a good candidate for packaging material. However, the harsh conditions required for its regeneration deteriorate the crystal structure of silk films, resulting in insufficient barrier properties for practical use. In this work, we prepared silk/cellulose nanocrystal (CN) composite films containing different CN loadings and investigated the changes of crystal structure according to the incorporation of rod-like nanoparticles with exceptional strength and modulus, as well as the mechanical and barrier properties of the composite films.

Resume : Photodynamic therapy (PDT) has proven to be a promising alternative for treating different types of cancers. The preferential sites of photodynamic action are the cell membranes, but the underlying mechanisms involved in membrane lipid oxidation are not fully understood. In order to investigate these mechanisms, suitable methods are required not only to mimic the cell membrane but also to obtain specific molecular information. Langmuir monolayers of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were applied here as cellular membrane mimetic systems to unravel the adsorption mechanisms of the photosensitizer erythrosin towards the membrane and the molecular-level effects that follow lipid oxidation. It was found that erythrosin adsorbs to the monolayer driven by attractive electrostatic interactions with the choline groups of both DOPC and DPPC. Upon irradiation, the modifications of DOPC monolayers are consistent with the hydroperoxidation process. Nevertheless, low levels of cytotoxicity were found in PDT experiments with in vitro culture of cells derived from oropharyngeal cancer (HEp-2), incubated with different concentrations (10-3 – 10-6 mol/L) of erythrosin in dark. Ongoing experiments of cytotoxicity upon irradiation have shown promising results in terms of photo-induced cell death, revealing the potential of erythrosin as photosensitizer in PDT applications.

Resume : With increasing environmental awareness, biopolymers from renewable resources such as poly(butylene succinate) (PBS), polycaprolactone, poly(hydroxy acid), and poly(lactic acid) have attracted much attention as replacements for conventional petroleum-based synthetic plastics. However, the practical use of these biopolymers is limited by their insufficient performance and relatively high cost as compared to those of petroleum-derived plastics. The preparation of composites with nanomaterials has been proposed as an alternative method to enhance the material properties of biopolymers. Cellulose nanocrystals (CNs), which are rod-like nanoparticles, are one of the most promising reinforcements in bio-nanocomposite materials because of their renewable nature, as well as their exceptionally high specific strength and modulus, low density, chemical tunability, and low cost. However, the number of hydroxyl groups in CNs makes it difficult to achieve acceptable dispersion levels of nanofillers in the nonpolar plastic matrix. In the present study, we performed surface modification of CNs by the acetylation method in order to enhance dispersion and we prepared PBS/CN nanocomposites. The influence of the CN loading level (from 0.1 to 1) and the degree of substitution (from 0.04 to 2.77) on the microstructure and morphology, as well as on the mechanical properties and biodegradability of the nanocomposites, was investigated.

Resume : The electrospinning was employed for preparation of nanofibrous membranes that have high potential application in tissue engineering. Nanofibers were electrospun from polycaprolactone (PCL) and polyethylene glycol (PEG). The used polymer solution with various ratios of PCL:PEG polymers ranging from 5:95 to 75:25 influenced the structure, mechanical properties and biodegradability of the nanofibers. The X-ray photoelectron spectroscopy revealed that by changing the PCL:PEG ratio in the original solution, the chemical composition and thus also properties of final electrospun polymer varied. Already a small addition of PCL improved the mechanical properties significantly although the degradation in water resembled rather the results for PEG material. In order to improve the biocompatibility of the nanofibers a thin amine layer by means of the cyclopropylamine plasma polymerization in radio frequency capacitively coupled discharge was deposited on prepared nanofibrous membranes. The presence of the amine groups is supposed to enhance the adhesion and proliferation of the cells, thus enhancing the properties of nanofibers for biomedical applications. The coating of nanofibers by a thin amine film resulted also in slight modification of mechanical properties and improved water stability of PEG-like membranes.

Resume : This study reports on the development and characterization of a carbonic anhydrase (CA)-based biocatalyst encapsulated in a biosilica matrix for use in CO2 sequestration. Encapsulation occurred simultaneously with autonomous silica synthesis by silica-condensing R5 peptide that was fused to recombinant CA. The encapsulation efficiency was greater than 95%, and the encapsulated CA was not leached from the silica matrix, demonstrating the highly efficient R5-mediated auto-encapsulation process. The catalytic efficiency for CO2 hydration was pH dependent, suggesting that proton transfer from silica to water is a rate limiting step for the fast catalysis. In addition to good reusability, the encapsulated CA exhibited outstanding thermostability, retaining 80% activity after 5 days at 50˚C. The thermoactivity was also remarkable, showing ~10-fold higher activity at 60˚C compared to that at 25˚C. The physical structure was observed to be highly compact with a low surface area, stressing the importance of the outermost surface for catalytic performance. We also demonstrated the applicability of the silica nanoparticle to the sequestration of CO2 in carbonate minerals. The rate of CaCO3 precipitation was remarkably accelerated by the encapsulated biocatalyst. Thus, this silica-CA nanocomposite, efficiently synthesized via a biomimetic green route, can be successfully used as a robust biocatalyst for biomimetic sequestration of the greenhouse gas CO2.

Resume : Bioelectronic devices have potential diagnostic and therapeutic applications in diverse medical fields such as the bionic ear and brain-computer interface. Electrode between the biotic and abiotic worlds has been demonstrated to be the most important part of these devices. However, implanting electrode inside the nervous system often incurs inflammatory response, which will lead to fibrous encapsulation, cutting off the connection between electrodes and electro-active cells and increasing the electrical impedance of the bioelectronics interface. Consequently, there is a high expectation for electrode coating of low impedance, high selectivity, high resolution and long-term stability. In early research, we have successfully developed a biomimetic conducting polymer film to facilitate a selective interaction to neural cells.1 However, the recording site is not the only part of an implanted electrode. The Insulating layer occupies the most part of the electrode, which plays very important role in the biocompatibility of the whole electrode. Therefore, we synthesized a protein/cell resistant poly(p-xylylene) thin film for the dielectric barrier. The design of bionic insulation significantly reduces the nonspecific adhesion of proteins/cells. We further integrated the biomimetic PEDOT derivatives with the bionic insulating material to fabricate an electrode array of all biomimicking polymers. We demonstrated that the feature of all biomimicking design ensures not noly a excellent proteins/cells resistance for the whole electrode but also a selective electrical interfacing of recording sites to neural cells. Reference: 1. B. Zhu, S.-C. Luo, H. Zhao, H.-A. Lin, J. Sekine, A. Nakao, C. Chen, Y. Yamashita and H.-h. Yu, Nature communications, 2014, 5.

Resume : At present, superparamagnetic (SPM) nanoparticles are being used in a variety of biomedical applications in order to facilitate both laboratory-based diagnostics, as well as therapeutic and diagnostic applications in-vivo, e.g., localised drug delivery. This is due to their high magnetic susceptibility, biocompatibility and tuneable characteristics. In this research, SPM iron oxide nanoparticles (NPs) are being applied in the development of a non-invasive method for protein biomarker detection in interstitial environments. The extracellular matrix (ECM), which is situated beneath the skin, contains a wide variety of compounds, fluids and proteins. The interstitial fluid within this matrix is understood to contain a wealth of biomarkers at concentrations ranges significantly higher than that in blood. (1) Thus, it is of increasing interest to develop new approaches to diagnostics for interstitial fluid given it can be accessed in a minimally-invasive manner and is known to contain a host of biomarkers. (2) Hence, the goal of this research is to establish a method to characterise the NP motion under magnetic field in viscous media (where viscosity ranges are similar to that of the ECM), and use this method to elucidate the factors that affect rates of NP velocity. In this research, an agarose hydrogel is employed as the viscous media. The movement of NPs under magnetic field through this media is monitored using an imaging technique. The primary forces influencing magnetic NP mobility in a biological system are the drag force (FD) and the external magnetic force (FM). It is critical to have stable, mono-disperse and biocompatible NPs, whose presence in-vivo does not generate an immune response and whose movement through the ECM can be controlled using an external magnetic field. Thus, the influence of core size and surface coating chemistry on mobility and stability in viscous media is investigated using our method. This presentation will highlight key results towards the development of functional NPs for potential biotargeting applications in the future. References: (1) Pavel Gromov, Irina Gromova, Charlotta J. Olsen, Vera Timmermans-Wielenga, Mai-Lis Talman, Reza R. Serizawa, José M.A. Moreira. (2013). Tumor interstitial fluid ? A treasure trove of cancer biomarkers. Biochimica et Biophysica Acta. 1834 (1), p2259?2270. (2) Sam J. Kuhn, Dennis E. Hallahan, and Todd D. Giorgio. (2006). Characterization of Superparamagnetic Nanoparticle Interactions with Extracellular Matrix in an in Vitro System. Annals of Biomedical Engineering. 34 (1), p51-58.

Resume : Bone losses often happens in aging population. Serious bone losses could resulted in various complicated damages, and orthopedic implant becomes inevitably. Metal materials were commonly used in artificial substitutes and human body assembly parts. Although currently many metal materials have clinical success for implant, there are many factors for the reliability of implants which includes wear, fatigue failure and corrosion. Careful selection of alloying additions when design new alloys for biomedicine can improve properties of corrosion, increased strength and wear resistance, decreased Young's modulus, etc. In this research, Ti-based metallic glasses were studied. The materials were melted then passed through a mold Rod size of about 3 ~ 6 mm were produced. The surface morphology and lattice structure of the alloying elements were observed by X-ray diffractometer and scanning electron microscopy. Dynamic tensile and static mechanical properties of Ti-based bulk metallic glass materials were investigated by means of a Brazilian disc method (BD) using a material testing system and a Split Hopkinson Pressure Bar, respectively. The mechanical and mechanical properties of the materials were mainly tensile strength and strain and stress. Dynamic and static fracture process of the Ti-based bulk metallic glasses at various loading rates was measured. Ti-based metal glass has a lower Young's modulus than human bone and high strength properties and good corrosion resistance; it has great potential as human bone implant material.

Resume : Stent is an essential medical device to prolong survival when plaque blocks body conduits or tubular organ. However, a conventional bare-metal stent (BMS) has been faced with restenosis problem caused by tissue hyperplasia secondary to BMS placements. Drug-eluting stent (DES) has been introduced to lower rate of restenosis. Especially reservoir-based DES has attracted lots of attention due to advantages of high capacity and uniformity of drugs. However, it is hard to fabricate reservoir structure with simple and time-efficient process. In addition to DES, to treat restenosis, controlling of the cell behavior that interact with implanted bio-devices has been also considered as desirable strategy because there is a need to limit the adhesion and viability of cells on stent. In order to effectively inhibit restenosis, we suggest multifunctional DES combined physically cell repellent approach with drug treatment using nanoturf structure. An ultraviolet (UV)-curable polysiloxane acrylate (PSA) is used to fabricate multifunctional nanostructure using two consecutive steps: UV induced polymerization and reactive ion etching (RIE) with time-efficient process because it demands only a few minute to fabricate. We elucidate tumor cell-repellent property by showing reduced focal adhesion and monitor number of attached tumor cells on the nanoturf structures compared with flat surface while maintaining biocompatibility. Furthermore, we showed the possibility of localized drug elution via near-infrared (NIR) irradiation. Our study has a great potentials to widen other biomedical implants that use a surface needed to control cell behavior and release a drug

Resume : The design concept to create the stimuli responsive photoactive at visible range carbon tubes nanostructures is based on constructed molecular models for the photoemission of semiconductor carbon nanotubes (CNT’s) functionalized by attached to the core and ends photoactive molecular complexes: metal (d - transition metal Cu) - organic (azole ligand) complex or by this complexe with coordinative bonded biomolecule (histidine). The tubes are the building blocks for nanostructures organization due to bonds between the metal ions and the ligands or the histidine molecules at different tubes. The architecture (SEM images) and the photoemission (PL spectroscopy) for nanostructures from these functionalized MWCNT in adsorbed layer at silicon substrate are characterized. The SEM images for this layer are interpreted using proposed molecular architectures models for building blocks connected through Cu2+ with attached two ligands molecules at different tubes cores and these bonds are partially retain in the complexes with coordinative bonded histedine molecules that can decrease formation of these structures due to their adsorbing on tubes. These layers with namely one and both two types of nanostructures are characterized by photoemission wide bands, having different intensities and different three subbands in visible range

Resume : To learn more about neurological diseases such as stroke, Parkinson’s and dementia, it is of upmost importance that neuronal behaviour and electrical activity of 3D neural networks is understood. Present electrophysiological techniques using 2D microelectrode arrays (MEAs) allow for extracellular recording of non–specific collections of neurons. 3D electrodes are highly desirable as they allow for a better electrode–neural interface, with a larger surface area and the ability to record from within the cell. Current optimisation of MEAs is ongoing, and devices, which are able to facilitate location traced simultaneous recording and stimulation of large populations of individual neurons, are required. Boron–doped nanocrystalline diamond (BNCD) coated carbon nanotubes (CNTs) have shown to be an attractive choice of material for neural interfacing due to the low impedance, high capacitance and biocompatibility observed[1], [2]. Here at UCL, CNT growth, which is performed in a DC plasma CVD process, is optimised in order to produce both patterns of vertically aligned and individual CNTs for intra–cellular recording application. Since combining individual BNCD coated CNT electrodes with 3D hydrogels is planned, controlled location and size of CNTs is desired. Therefore, we have developed recipes in which specific dimensions of CNTs can be grown, followed by diamond coating. [1] G. Piret, C. Hebert, J. P. Mazellier, L. Rousseau, E. Scorsone, M. Cottance, G. Lissorgues, M. O. Heuschkel, S. Picaud, P. Bergonzo, and B. Yvert, “3D-nanostructured boron-doped diamond for microelectrode array neural interfacing,” Journal of Neuroscience Methods, vol. 53, pp. 173–183, Jun. 2015. [2] A. C. Taylor, B. Vagaska, R. Edgington, C. Hebert, P. Ferretti, P. Bergonzo, and R. B. Jackman, “Biocompatibility of nanostructured boron doped diamond for the attachment and proliferation of human neural stem cells,” J. Neural Eng., vol. 12, no. 6, p. 066016, Dec. 2015.

Resume : Self-assembled nanotubes and nanofibers from organic molecules such as peptides have many possible applications in biomedicine [1]. In this paper, uniaxially aligned epitaxial nanofibers from semiconducting para-quaterphenylenes are investigated. They are formed by self-assembly after vacuum deposition. These nanofibers have already been applied for organic electronics, but can serve as active and passive templates for biological uses. Functionalization controls many of their properties [2,3]. Methoxy- and cyano-functionalization are of special interest due to the asymmetric charge distribution. Here, nanofibers from in the 4,4’’’ positions cyano- and methoxy-functionalized para-quaterphenylenes (CNP4, CNHP4, MOP4) on muscovite mica and HOPG are studied. Thin-film phases are identified by X-ray diffraction. Their optical properties, their morphology, and their electric surface potential with and without illumination differ, reflecting different polymorphs, facets, and contact faces. REFERENCES. [1] I.W. Hamley, Angew. Chem. Int. Ed. 53, 6866-6881 (2014). [2] F. Balzer, Ch. Röthel, H.-G. Rubahn, A. Lützen, J. Parisi, R. Resel, M. Schiek, J. Phys. Chem. C 120, 7653-7661 (2016). [3] F. Balzer, M. Schulz, A. Lützen, M. Schiek, Soft Matter 12, 9297-9302 (2016).

Resume : Optical properties of biomolecules have been extensively investigated for many decades in order to find intrinsic optical biomarkers. Recently, intrinsic fluorescence has been found in a variety of bioinspired peptide nanostructures [1-3]. In this work we report on the aggregation properties of an amphiphilic peptide, the (Ala)10-(His)6, denoted in the following as A10H6, by AFM and fluorescence measurements. We found that this peptide is able to form amyloid-like fibrils above a critical aggregation concentration[4]. Interestingly, by fluorescence microscopy measurements we observed an intrinsic fluorescence of these supramolecular peptide nanostructures in the visible range. Steady state and time resolved fluorescence measurements have been performed in solution at different A10H6 peptide concentrations and using different solvents, in order to correlate the measured fluorescence intensity to the aggregation process and to the morphology of the nanostructures obtained. The possibility to obtain intrinsic fluorescence from peptide nanostructures would pave the way to develop a new generation of bio-inspired optoelectronic nanomaterials for nanophotonic applications. REFERENCES. [1] Del Mercato L. L., Pompa P., Maruccio G., Della Torre A., Sabella S., Tamburro A. M., Cingolani R., Rinaldi R. PNAS 104, 18019-18024 (2007). [2] Chan F. T. S., Kaminski Schierie G. S., Kumita J. R., Bertoncini C. W., Dobson C. M., Kaminski C. F. Analyst 138, 2156-2162 (2013). [3] Handelman A., Kuritz N., Natan A., Rosenman G. Langmuir 32, 2847–2862 (2016). [4] Hamley I. W., Kirkham S., Dehsorkhi A., Castelletto V., Adamcik J., Mezzenga R., Ruokolainen J., Mazzuca C., Gatto E., Venanzi M., Placidi E., Bilalis P., Iatrou H. Biomacromolecules 15, 3412−3420 (2014).

Resume : Supported lipid membranes represent an elegant way to design smart fluid biointerfaces able to mimic the physico-chemical properties of biological membranes, providing an excellent model system for studying the surface chemistry of the cell. Furthermore, supported lipid membranes are accessible to a wide variety of surface-specific analytical techniques, providing smart biointerfaces for biotechnological applications,1 such as the design of chemical and biomedical sensors. In this contribution we describe a new lipid-based sensor for the detection of the thymidine phosphorylase (TP) enzyme, one of the most known biological markers of solid tumors. This enzyme promotes tumor growth and metastasis and is overexpressed in the presence of cancers, so that also its blood levels increase.2 To achieve this goal, one of the most used anticancer drugs, i.e. the pyrimidine analogue 5-fluorouracil (5-FU)3 has been properly functionalized with a C-12 aliphatic chain in order to be inserted into gold supported lipid membranes. The interaction of TP with the 5-FU inhibitor and its derivatives has been firstly evaluated in solution by fluorescence measurements, then the derivatives have been inserted into a lipid bilayer linked to a gold surface. The supported lipid biointerfaces have been characterized by ellipsometry, AFM and electrochemical techniques. The TP interaction with the substrate has been quantitatively evaluated by quartz crystal microbalance, following the oscillation frequency of the QCM crystal, making this system a very promising sensor for the detection of TP concentration in blood. REFERENCES. 1Castellana, E. T.; Creme, P. S. Solid supported lipid bilayers: From biophysical studies to sensor design. Surface Science Reports 61, 429–444 (2006). 2Haraguchi, M.; Komota, K.; Akashi, A.; Furui, J.; Kanematsu, T. Occurrence of hematogenous metastasis and serum levels of thymidine phosphorylase in colorectal cancer. Oncol. Rep. 10, 1207-1212 (2003). 3Malet-Martino, M.; Martino, R. Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. The Oncologist 7, 288-323 (2002).

Resume : The design and optical characterization of the protein amino - acids is key for understanding of the amino-acids molecules behaviour as basis sequences of biological macromolecules ( proteins) and their using as photoactive molecules, for example, in cell level biomaterials or advanced photovoltaic systems for an energy sources [1]. Therefore, we have started to design amino-acids molecules and have studied classic models for light excited electron transition through LUMO-HOMO band gap for the molecules and discuss ones using theories for LUMO-HOMO band gap formation for these molecules having different confirmations [2]. Then we selected amino-acidmolecule for studies by the PL spectroscopy taking in account that we can use the laser with 408 nm wavelength (3.3 eV) for experiments. The cysteine PL excited by the laser with wavelength 408 nm (3.3 eV) is characterized by the band in 1.5- 2.7 eV range. This band includes subbands that are centered at 2.04, 2.24 and 2.4 eV. The present of subbands are explained by the dependence on the conformation of the molecule geometry in the cysteine layer of the HOMO-LUMO value as it is found due to comparison of these subbands with calculations of electronic excitations of the cysteine conformers [2]. Therefore it is possible to use light excited electron transitions in the cysteine layer with different molecule geometry in photonic systems. 1. Koo, Suk Tai Chang, Joseph M. Slocik, Rajesh R. Naik and Orlin D. Velev, Aqueous soft matter based photovoltaic devices, J. Mater. Chem., 2011. 2. R.Maul, M. Preuss, F. Ortmann, K. Hannewald, and F. Bechstedt, Electronic Excitations of Glycine, Alanine, and Cysteine Conformers from First-Principles Calculations, J. Phys. Chem. A 2007, 111, p.4370-4377.

Resume : Single-molecule detection(SMD) is a novel technique by which signals and activities of individual molecules can be captured and perceived in real time. Apart from using biological nanopores and inorganic solid-state nanopores, quartz nanopipettes have more striking features—entirely signal read-out, simple fabrication and commercial production in SMD. However, it is quite hard to detect small molecules like proteins using nanopipettes due to large tip diameters. So in this project, a Y-shaped DNA-aptamer complex is fabricated to attach to target proteins. In this way, the signals of the whole aptamer-protein complex could be distinguished during translocation.

Resume : Nitrogen compounds (NH3, NH4 +) and sulfur oxides (SO2) in many cases are used as indicators of the quality and freshness of food, the presence of high concentrations of nitrogen monoxide (NO) in exhaled air may indicate lung disease or cardiovascular system, ammonia (NH3 ) - about the presence of gastric ulcers caused by Helicobacter pylori. The purpose of this work is to study the sorption properties of sensors based on porous silicon to spray compounds that contain atoms of nitrogen, sulfur, carbon: NO, NH3, NH4 +, SO, SO2, CO, CO2 and others. Meso- and nano-porous silicon treated by pre-processing silicon wafers in ammoniac-peroxide and acid-peroxide solutions by various methods combined with the subsequent formation of anodic porous silicon surface for different values of anode current. As shown by previous studies, under certain conditions of the formation of the porous layer the linear dependence of sensor surface potential on the concentration of ammonia can be obtained. Porosity silicon surface after anodizing studied by methods of metallography and scanning electron microscopy. Study of sorption properties of sensors surface by spectral, photometric and electrophysical methods was carried. The sensitivity of the analog path of computerized measuring system was provided at one pico Ampere. Measurement error and processing did not exceed 8%. According to the research, the structure and method for measuring and express analysis of content in air of compounds nitrogen, sulfur, carbon for tasks of food safety, biotechnology and medicine were proposed.

Resume : A set of thymine-functionalized chromophores such as tetraphenylporphyrin, azobenzene and carbon quantum dots were synthesized and studied in terms of their self-recognition abilities to generate ordered nano-architectures. Additionally, fully adenine-capped, water soluble, gold nanoparticles were synthesized and properly characterized. In particular, even we observed a strong self-recognition between thymine-thymine systems, the fully functionalized adenine-capped nanoparticles act as a “breaking” molecular binder thus to allow the complementary recognition with the thymine-functionalized chromophores and the consequent molecular reorganization. It was found that adenine-thymine binding, occurring between these complementary self-organized complex systems, allowed the formation of precisely assembled nano-systems that powerfully depend in their morphologies from the nature of the chromophores utilized. These well organized supramolecular architectures are able to undergo to morphologically self-shaping process under illumination by visible light, through the activation of the plasmon resonance of gold nanoparticles which selectively affected, and precisely rearranged, the binding modes of the self-assembled microstructures at the nanoscale level. Finally, these studies were extended to the selective molecular recognition at the surface, confirming the high binding affinity of these complex systems even at this level.

Resume : The present investigation, a detailed study of corrosion behavior and bio-activity of titanium based foam developed by powder metallurgy route has been carried out. Titanium based foam has been developed by powder metallurgy route using cenosphere, NaCl and NH4CO3 as space holders under optimum processing conditions. Followed by processing, a detailed characterization of the microstructure and phase of the composite has been carried out. The corrosion behaviour of the samples has been evaluated in Hank’s solution (CaCl2: 0.14g, MgSO4•7H2O: 0.1g, MgCl2.6H2O: 0.1g, Na2HPO4.2H2O: 0.06g, KH2PO4: 0.06g, glucose: 1.0g, NaHCO3: 0.35g and rest H2O to 1000 ml) by potentiodynamic polarization technique. The detailed objectives include understanding the role of space holders on the characteristics (microstructure, phase, composition, porosity) and corrosion behavior of the foamed coupons. In addition, the bioactivity behavior of the samples has also been evaluated by dipping it in Hank’s solution and subsequently, measuring the weight change and apatite deposition rate at regular interval. The future scope of development of nano-porous titanium foam has also been presented.

Resume : Fouling of materials in a marine environment is caused by the accumulation of microscopic and subsequently macroscopic organisms to their surface. Strategies for mitigating and controlling this process are interesting for both commercial and environmental reasons as fouling results in decreased materials performance, increased maintenance and cleaning costs in addition to increased concentration of pathogenic species in localised areas. Traditional methods of biofouling reduction involve application of biocidal coatings (e.g. metals or oxides) which are gradually released into the marine environment and can result in long term environmental problems, therefore development of environmentally-friendly, non-biocidal antifouling methods is paramount. Herein we report on the performance of carbohydrate thin film coatings for fouling reduction on alloys and polymeric materials commonly utilised in marine applications. Covalent attachment of carbohydrates was first studied on model surfaces using surface spectroscopies and microscopy. The performance of the coatings was studied in a coastal marine environment. Comparative analysis in addition to microscopy results suggest significant reduction in biological fouling compared to unmodified controls.

Resume : From more than a decade it is known that Alzheimer disease is associated with the formation of plaques and tangles in the brain. The affecting levels of plaque increases for long time, up to 30 years, before clinical signs of Alzheimer disease appear. Amyloid beta peptides are involved in Alzheimer disease, forming insoluble and highly ordered linear aggregates, that grown into plaques. Compounds that selectively interfere with the molecular steps along the aggregation path are denominated amyloid inhibitors. Recent works by Shukla [1] and Chan [2,3] demonstrated that amyloid peptides can show intrinsic florescence in the visible wavelength region due to aggregation. Additionally structure-specific fluorescence lifetimes were observed. In this work we propose to study the influence of amyloid inhibitor compounds in the kinetics of fibril formation, by following both the steady-state and time-resolved aggregation-intrinsic visible florescence. Following noninvasively beta-amyloid fibril formation inhibition by the aggregation-intrinsic visible florescence offer a label-free method to test amyloid inhibitors and also envisages the possibility of the use of photonic devices in the early detection and treatment monitoring of amyloid related diseases. REFERENCES [1] A. Shukla et al, Arch Biochem and Biophys 425 (2004) 144. [2] F. T. S. Chan et al, Analyst 138 (2013) 2156. [3] D. Pinotsi et al, ChemBioChem 2013, 14, 846. Acknowledgements: This work has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 654148 Laserlab-Europe.

Resume : Learning from nature and based on lotus leaves and fish scale, we developed super-wettability system: superhydrophobic, superoleophobic, superhydrophilic, superoleophilic surfaces in air and superoleophobic, superareophobic, superoleophilic, superareophilic surfaces under water [1]. Further, we fabricated artificial materials with smart switchable super-wettability [2], i.e., nature-inspired binary cooperative complementary nanomaterials (BCCNMs) that consisting of two components with entirely opposite physiochemical properties at the nanoscale, are presented as a novel concept for the building of promising materials [3-4]. The smart super-wettability system has great applications in various fields, such as self-cleaning glasses, water/oil separation, anti-biofouling interfaces, and water collection system [5]. The concept of BCCNMs was further extended into 1D system. Energy conversion systems that based on artificial ion channels have been fabricated [6]. Also, we discovered the spider silk?s and cactus's amazing water collection and transportation capability [7], and based on these nature systems, artificial water collection fibers and oil/water separation system have been designed successfully [8]. Learning from nature, the constructed smart multiscale interfacial materials system not only has new applications, but also presents new knowledge: Super wettability based chemistry including basic chemical reactions, crystallization, nanofabrication arrays such as small molecule, polymer, nanoparticles, and so on [9]. Reference: 1. (a) Adv. Mater. 2014, 26, 6872-6897.. (b) J. Am. Chem. Soc. 2016, 138, 1727-1748. 2. Adv. Mater. 2008, 20 (15), 2842-2858. 3. Pure Appl. Chem. 2000, 72 (1-2), 73-81. 4. Small. 2015, 11, 1071-1096. 5. Adv. Mater. 2011, 23 (6), 719-734. 6. (a)Chem. Soc. Rev. 2011, 40 (5), 2385-2401; (b) Acc. Chem. Res. 2013, 46 (12), 2834-2846; (c) Adv. Mater. 2010, 22 (9), 1021-1024. (d) ACS Nano 2009, 3 (11), 3339-3342; (e) Angew. Chem. Int. Ed. 2012, 51 (22), 5296-5307; 7. (a) Nature 2010, 463 (7281), 640-643; (b) Nat Commun 2012, 3, 1247. 8. (a) Nat Commun 2013, 4, 2276; (b) Adv. Mater. 2010, 22 (48), 5521-5525. 9. (a) Chem. Soc. Rev. 2012, 41 (23), 7832-7856; (b) Nat. Commun. 2015, 6, 6737. (c) Adv. Funct. Mater. 2011, 21 (17), 3297-3307; (d) Adv. Mater. 2012, 24 (4), 559-564; (e) Nano Research 2011, 4 (3), 266-273; (f) Soft Matter 2011, 7 (11), 5144-5149; (g Soft Matter 2012, 8 (3), 631-635; (h) Adv. Mater. 2012, 24 (20), 2780-2785; (i) Adv. Mater. 2013, 25 (29), 3968-3972; (j) J. Mater. Chem. A 2013, 1 (30), 8581-8586; (k) Adv. Mater. 2013, 25 (45), 6526-6533

Resume : Spiders achieve superior silk fibres by controlling the molecular assembly of silk proteins and the hierarchical structure of fibres. However, current wet-spinning process for recombinant spidroins oversimplifies the natural spinning process. Here, water-soluble recombinant spider dragline silk protein (with a low molecular weight of 47 kDa) was adopted to prepare aqueous spinning dope. Artificial spider silks were spun via microfluidic wet-spinning, using a continuous post-spin drawing process. By mimicking the natural spinning apparatus, shearing and elongational sections were integrated in the microfluidic spinning chip to induce assembly, orientation of spidroins, and fibril structure formation. The additional post-spin drawing process following the wet-spinning section partially mimics the spinning process of natural spider silk and substantially contributes to the compact aggregation of microfibrils. Subsequent post-stretching further improves the hierarchical structure of the fibres, including the crystalline structure, orientation, and fibril melting. The tensile strength and elongation of post-treated fibres reached up to 510 MPa and 15%, respectively. This spinning process is economic and non-toxic, compared to traditional wet-spinning of recombinant spider silk. It also breaks the molecular weight limitation to reap artificial fibre with high strength.

Resume : Polymeric hydrogels with high mechanical strength are the important soft-wet materials for the applications in pharmaceutics, biomedical and industrial fields. Our group of Functional Nanocomposite Gel was founded in 2011 at School of Chemical Science and Engineering, Tongji University. The current research focus on the mild preparation and 3D printing of hydrogel via enzymatic polymerization. The hydrogels and nanogel crosslinked at physiological condition are mainly applied as tissue engineering and bioimaging, respectively. We also design gel electrolyte by in-situ photo-polymerization for the application in energy devices.

Resume : Poly(3,4-ethylenedioxythiophene) or PEDOT has been demonstrated in various biomedical applications, ranging from biosensing to medical bionics. Being a conductive biointerface, PEDOTs can be served as an electrode for either electrochemical biosensing or to provide electrical stimuli on attached biomolecules. The functional groups on PEDOTs play an important role for the modification of surface property. In this presentation, I would like to introduce our strategies to manipulate the surface properties of PEDOT thin films for detection applications. The control of surface charge can enhance the interaction between charged biomolecules, such as dopamine, and PEDOT surfaces through coulomb force, which leads to a higher detection of these biomolecules. The recognition between specific compounds and functional groups, including phosphorylcholine and boronic acid groups, can also be used for the detection purpose. The recognition process between these functional groups on PEDOT thin films and targeted biomolecules are generally identified by using a quartz crystal microbalance. The attached biomolecules usually alter the charge distribution on PEDOT surfaces, which can also be measured by using an electrochemical technique.

Resume : Advances of bioelectronics towards high-resolution communication and long-term implantation are reaching limitations of traditional materials such as metals and silicone. An ideal electronic material combining softness, biofunction, and low impedance is desired to meet the required biocompatibility and electrical trade-offs for interfacing with cells/tissues. Toward this aim, we developed a series of cell membrane mimicking EDOT polymers, which combining biofunction with low impedance. These conducting polymers present a high selectivity of interaction to targeted cells and proteins. The selective interaction could be well controlled to be static, dynamic or even 3-dimensional by defining various structures for building blocks. All these materials demonstrated an intimate, stable and efficient electrical interface with targeted cells, which is ensured by integrating nonspecific-binding resistance, specific interaction and low-impedance into one PEDOT polymer. To ensure integrity of the bioinspired PEDOTs on electrodes in long term stimulation, we further developed a series of bioinspired PEDOTs with a very strong adhesion to electrode substrates. The electrodes of the bioinspired PEDOTs demonstrated their long-term stability to functionalize in aqueous buffer at low impedance.

Resume : Conducting polymers had been widely used in the fields of cell-related diagnostic and therapeutic platforms. Among them, researchers showed great interests on poly(3,4-ethylenedioxythiophene) (PEDOT) due to its excellent properties of low structure defects, high aqueous stability and biocompatibility. Meanwhile, properly nanostructures could extremely enhance the tumor cell-capturing efficiency of bio-functional PEDOTs1. Several approaches have been made to fabricate PEDOT materials with nanostructures via template method, seeding, interfacial polymerization, vapor polymerization, and self-assembly approach. However, most of them require hard-templates or surfactants, which would complicate the preparation process and reduce the quality of the obtained materials. Therefore, we have proposed the approach for fabricating template-free bio-functional poly(3,4-ethylenedioxythiophene) with controllable nanostructures via electrochemical deposition. By tuning the experimental condition, controllable switching nanodots and nanotube structure of PEDOT, PEDOT-OH and PEDOT-COOH could be fabricated. Meanwhile, changing of electric charges and physical structures of nanodots and nanotube PEDOT-OH films were studied to explain the morphology transformation. Besides, the cell-capturing efficiency was characterized of the nanodots and nanotube structure EDOT-COOH films after bio-conjugated. We hope this current study would provide a simple and effective method for fabricating high efficiency tumor cell-capturing materials. Reference: 1. Sekine J., Luo S-C, Wang S.,Zhu B., Tseng H-R and Yu H-H, Functionalized Conducting Polymer Nanodots for Enhanced Cell Capturing: The Synergistic Effect of Capture Agents and Nanostructures, Adv. Mater. 23, 4788–4792 (2011).

Resume : Biodegradable and biocompatible elastomers (bioelastomers) could resemble the mechanical properties of extracellular matrix and soft tissues, thus, are very useful for many biomedical applications. Despite the significant advances, tough bioelastomers with fatigue resistance, self-recovery, shape memory properties, good biocompatible and biodegradability has remained elusive. Here, we report a new design concept of bioelastomers with aforementioned advantages via bioinspired sacrificial bonds. We graft2-ureido-4[1H]-pyrimidinones (UPy) units with strong self-complementary quadruple hydrogen bonds to covalently crosslinked poly(sebacoyl diglyceride) (PSeD),[1] refined version of a widely used bioelastomer poly(glycerol sebacate) (PGS). The covalent crosslinks maintain the structural integrity of resultant PSeD-U bioelastomers compliant to dynamic mechanically environment. The reversible hydrogen bonds perform several mechanical functions simultaneously: toughening the bioelasomters and enhancing the tearing resistance (tearing energy of 3800 J/m2) via energy dissipation during bond rupture, and enabling the fatigue resistance and nearly 100% self-recovery during cyclic deformations by bond re-formation. PSeD-U bioelastomers can be tuned over a wider range by changing covalent crosslinking density and the grafting ratio of UPy unit. Furthermore?PSeD-U bioelastomers exhibit shape memory properties, and good biocompatibility and biodegradability. [1] You Z, Cao H, Gao J, Shin PH, Day BW, Wang Y. A functionalizable polyester with free hydroxyl groups and tunable physiochemical and biological properties. Biomaterials. 2010;31:3129-38.

Resume : Silk fibroin is a good candidate to fabricate conductive biomaterial for bioelectrical applications because of its excellent mechanical property, biocompatibility and biodegradability. The modification by conductive polymer can endow silk fibroin with novel conductive functionality. Poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT) and its derivatives are very potential for the modification due to the high conductivity, biocompatibility, environmental stability and light transmittance. However, the hydrophobic EDOT monomers have difficulties in absorbing and synthesizing on the surface of silk fibroin. In order to improve the efficiency of the polymerization, sodium dodecyl sulfate (SDS) was adopted as surfactant while ammonium persulfate (APS) was used as oxidant. Poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-OH) was polymerized and covalently deposited as a conducting layer on the surface of RSF film. The effects of the dosages of surfactant and oxidant, initial pH value and monomer concentration on the conductivity and morphology of the film were investigated. Results showed that SDS plays an important role to construct smooth conductive coating with several microns. The conductive RSF film shows a square resistance on the order of 105? or a conductivity on the order of 10-3 S/cm. This modification can be applied for RSF materials with various forms including fiber, film, foam, mats and 3D scaffolds. It is also possible to construct a microfluidic device with integrated conductive RSF channel for further applications of biosensor, tissue engineering and organic electronics.

Resume : Inspired by the strong chemical adhesion of mussels, polydopamine (PDA) was adopted for coating the insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) via a facile in situ polymerization of dopamine on the surface of explosive crystals. A robust and compact core-shell structure was confirmed by field-emission scanning electron microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS) results. After coating, the mechanical strength improved with PDA loading, due to the formation of highly effective crosslinked network. With a PDA coating content of 4.5%, the compressive and tensile strength of TATB/PDA composites were 46.9% and 65.4% higher than that of the TATB alone. Compared with neat TATB, a remarkable enhanced effect was observed in non-linear creep properties at different temperatures and stresses for TATB/PDA composites with reduced creep strain and constant creep rate. The nonlinear dependence of the creep strain on creep time was fitted by a six-element mechanical model. The mechanical enhancement mechanism could be originated from that dense and rigid PDA shell which constrains the expansion and the slide of the single layer of TATB energetic crystals. Due to the high rigidity and strong chemical adhesion of PDA on the crystal surface, PDA acts as a high pressure vessel to envelop TATB crystals. The preparation of core-shell structure explosive composites with bio-inspired PDA material provides an efficient route for the mechanical enhancement of high explosives.

Resume : Circulating tumor cells (CTCs) have become an emerging ?biomarker? for monitoring cancer metastasis and prognosis. Although there are existing technologies available for isolating/counting CTCs, the most common of which using immunomagnetic beads, they are limited by their low capture efficiencies and low specificities. By introducing a three-dimensional (3D) nanostructured substrate ? specifically, a silicon-nanowire (SiNW) array coated with anti-EpCAM ? we can capture CTCs with much higher efficiency and specificity. The conventional methods of isolating CTCs depend on biomolecular recognitions, such as antigen-antibody interaction. Unlikely, we here proposed that nanoscaled local topographic interactions besides biomolecular recognitions inspired by natural immuno-recognizing system. This cooperative effect of physical and chemical issues between CTCs and substrate leads to increased binding of CTCs, which significantly enhance capture efficiency. Recently, we have developed a 3D cell capture/release system triggered by enzyme, electrical potential and temperature as well as magnetic field, which is effective and of ?free damage" to capture and release cancer cells. In addition, immune cells have also been employed as living template for greatly improving the limitation of traditional immunomagnetic beads. Furthermore, the potential pollution from biochip waste can be successfully disposed by employing self-cleaning substrates. Therefore, these bio-inspired interfaces open up a light from cell-based disease diagnostics to subsequent safety treatment of biomedical waste. References [1] Liu X. L.; Wang S. T. Chem. Soc. Rev. 2014, 43, 2385. [2] Zhang P.; Chen L.; Xu T.; Liu H.; Liu X.; Meng J.; Yang G.; Jiang L.; Wang S. T., Adv. Mater., 2013, 25, 3566. [3] Huang C.; Yang G.; Ha Q.; Meng J. X.; Wang S. T. Adv. Mater. 2015, 27, 310. [4] Li Y. Y.; Lu Q. H.; Liu H. L.; Wang J. F.; Zhang P. C.; Liang H. G.; Jiang L.; Wang S. T. Adv. Mater. 2015, 27, 6848. [5] Zhang F. L; Jiang Y.; Liu X. L.; Meng J. X.; Zhang P. C.; Liu H. L.; Yang G.; Li G. N.; Jiang L.; Wan L. J.; Hu J. S.; Wang S. T. Nano Lett. 2016, 16, 766.

Resume : Biodegradable and biocompatible elastomers (bioelastomers) can mimic the mechanical properties of soft tissues, and sustain and recover from various deformations without mechanical irritations to the surrounding tissues when implanted in a mechanically dynamic environment in the body. Thus, bioelastomers have attracted great attentions in multiple biomedical applications including tissue engineering, drug delivery, and in vivo sensing [1]. However , it is still a challenging to produce ideal bioelastomers with good biocompatibility, biodegradability, processability, bioactivity, and mechanical properties. Herein, we will present our recent works on design and development of new bioelastomers with aforementioned advantages. Poly(glycerol sebacate) (PGS) is a representative of bioelastomers and has been widely used [2]. However, the limitations of its synthetic method lead to unsatisfied mechanical strength and inconvenient processing, which retard its further applications. We establish acid-induced epoxide ring-opening polymerization to produce poly(sebacoyl diglyceride) (PSeD), a refined version of PGS, with significantly improved structural regularity and mechanical properties [3-4]. Then, we construct supramolecular PSeD elastomers with good thermoplastic processabilities and self-healing properties by introducing dynamic hydrogen bond-based crosslinkings [5]. Furthermore, we yield more tough PSeD bioelastomers via dual crosslinking mechanism. In addition, we demonstrate the efficiency to tailor the bioactivity using small functional units in side groups, which represents a powerful way of practically producing therapeutic materials [6-7]. Then, 3D printing technology with special processes has been developed to fabricate elastic scaffolds with well-organized hierarchical porous structures, which exhibit a high efficiency on the treatment of myocardial infarction in a rat model. The design strategies, the synthetic and processing methods developed here are versatile and provide new tools to construct bioelastomers with expected properties for a wide range of biomedical applications. Reference: [1] You Z, Wang Y. Bioelastomers in tissue engineering. In: Burdick J, Mauck RL, editors. Biomaterials for tissue engineering applications: a review of the past and future trends: Springer-Verlag/Wien; 2011. p. 75-118. [2] Rai R, Tallawi M, Grigore A, Boccaccini AR. Prog. Polym. Sci. 2012; 37: 1051-78. [3] You Z, Cao H, Gao J, Shin PH, Day BW, Wang Y. A functionalizable polyester with free hydroxyl groups and tunable physiochemical and biological properties. Biomaterials 2010; 31: 3129-38. [4] You Z, Wang Y. Adv. Funct. Mater. 2012; 22: 2812-20. [5] Chen S, Bi X, Sun L, Gao J, Huang P, Fan X, You Z, Wang Y. ACS Appl. Mater. Interfaces 2016; 8: 20591-9. [6] Wang S, Jeffries E, Gao J, Sun L, You Z, Wang Y. ACS Appl. Mater. Interfaces 2016; 8: 9590-9. [7] Huang P, Bi X, Gao J, Sun L, Wang S, Chen S, Fan X, You Z, Wang Y. J. Mater. Chem. B 2016; 4: 2090-101.

Resume : Conductive polymers (CP), such as polythiophenes, polyanilines and polypyrroles, have been widely explored for applications including organic photovoltaic cells, organic electronics, supercapacitors and actuators. Free-standing CP films can be synthesized by electrochemical polymerization, while these films are often fragile and/or weak due to the rigid conjugated molecular structure. It is well known that animal dermis possesses a dynamic network structure consisted by rigid collagen fibers and soft elastin fibers, which interconnect through supramolecular interactions to form a dynamic network, making animal dermis a sturdy and flexible material. Inspired by the dynamic network structure of animal dermis, we have demonstrated that a dynamic network formed by supramolecular interconnection between a soft polymer and a rigid CP would yield a strong, tough and active CP-based composite material. The addition of soft polymer between rigid CP chains can help to enlarge the distance between rigid CP chains, which could enhance the motion of CP chain segment upon mechanical stress. From this point of view, the soft polymer serves as a plasticizer for CP. On the other hand, the supramolecular interactions such as dynamic covalent bonds, hydrogen bonds and electrostatic interactions between the soft polymer and CP are stronger than the van der Waals' force between typical plasticizer and plastics. Therefore, the soft polymer behaved as a dynamic crosslinking agent, which can greatly enhances the flexibility of CP with no compromise of the film's strength. Upon a large mechanical stress, the supramolecular interactions between soft polymers and rigid CP would break to dissipate destructive energy, which would greatly improve the toughness of the materials. Beyond the enhancement of mechanical properties, the dynamic nature of supramolecular interactions between soft polymer and rigid CP could also bring new properties to the CP-based composite material, such as stimuli-responsibility.

Resume : Abstract: Water is essential for life on earth and considered a symbol of purity. 71% of the surface of our planet is covered by water, and our own body is composed of 65% of this simple but vital molecule. Considering increasing environmental issues, the idea of replacing plastics with water-based materials, so-called hydrogels, seems quite reasonable. Here we developed photolatently modulable hydrogels, composed of a polymer network accommodating photocatalytic titania nanosheets at every crosslinking point. As titania nanosheets can utilize gelling water as their source of radicals, its long-lasting photocatalysis makes the hydrogels readily modulable. Furthermore, We developed a highly anisotropic hydrogel having a large compression resistivity and, in its orthogonal direction, an ultralow internal friction, so that this material, just like articular cartilage, efficiently insulates horizontal vibrations even under a heavy weight. We anticipate that the concept of embedding anisotropic repulsive electrostatics within a composite material, inspired by articular cartilage, will open up new possibilities for developing soft materials with unusual functions.

Resume : Antifouling modification technology is developed for many biomedical applications such as blood-contact devices and biosensors. In this work, a photo-reactive polymer containing zwitterionic carboxybetaine groups was prepared by copolymerization of two kinds of methacrylic acids with carboxybetaine and azidoaniline. The carboxybetaine moiety is for low fouling and the azidophenyl moiety is for photo-crosslinking. The synthesized copolymers were coated onto polymeric substrates, and then covalently immobilized on the substrates by exposure to UV radiation. The poly(CBMA-co-AzMA) coating revealed that cell and platelet adhesion and protein adsorption to the substrates were reduced significantly compared to the untreated substrate. Furthermore, the direct immobilization of galactrosamine was carried out on the polymer coating by EDC/NHS chemistry. The galactose-immobilized surface had the potential for selecting hepatocyte adhesion from co-population of differing cell types. In addition, the incorporation of photolithographic technology could make micropatterns of poly(CBMA-co-AzMA) coating for cell co-culture of hepatocytes and fibroblasts. This work demonstrates that the reported technique is an economic and facile tool for layers of reduced adsorption of protein modification with functional groups in one step.

Resume : Interfacing materials with cells through specific ligand/receptor interactions, matching mechanical properties, and matching nanostructures are very critical in biomedical technologies. Recently, conducting polymers have emerged for various related applications, ranging from biosensing to medical bionics. Many features of conducting polymers, including simplicity for nanostructure fabrication, tailored functional groups for bioconjugation, intrinsic electrical conductivity, and softer mechanical characteristics than metals, provide advantages as materials for cell-related diagnostic and therapeutic platforms as well as controlled cell engineering. The research of Yu Initiative Research Unit focus on the development of independent and multidisciplinary research program though the triangle of chemistry, electronic materials, and biomedical/biological investigations based on molecular and nano-assembled building blocks of conducting polymers. The organic conductive biomaterials we developed, unlike traditional polymers or inorganic metals/ceramics, provides a unique toolkit which integrates electrical control with all the known molecular and biomolecular building blocks required for bioengineering. Ultimately, it would provide a platform which can combine biochemical control, spatial arrangement, and matching mechanical characteristics with electrical stimulation or signaling. Nanostructures of conjugated materials have become one of the most important research topics in the research because of the nanostructure?s influence on the materials performance. Up to date, most research focus on the nanostructures and material properties of unfunctionalized ?-conjugated materials and limited studies on nanostructures of functionalized ones. Because of the molecular advantageous features of dioxythiophenes, we are particularly interested to develop general approaches for their polymeric nanostructures with various functional groups. We first enlarged the dioxythiophene-based monomer library with a variety of molecular building blocks. The monomers can be classified as two groups. Material modulation monomers are synthesized to manipulate the material properties, ranging from highly hydrophobic to highly hydrophilic, and create desired assemblies. The side chains included alkyl groups, perfluorinated groups, oligoethylene glycol groups, and especially zwitterionic phosphorylcholine and betain groups. Our research represents the first example in linking these biomimetic zwitterionic side-chains in conjugated materials to create enzyme/cell resistant conductive surface. The other group of monomers is the ones provide target function. For the biomaterials research, they provide the site for bioconjugation (-COOH, -NH2, -maleimide, -N3). The library now consists of >80 monomers with different linkers and functional groups. Mixing the monomers from two groups, we would achieve ?-conjugated materials with desired functions and material characteristics. For example, we combined the maleimide- and phophorylcholine-functionalized dioxythiophenes to construct conductive membranes. Upon bioconjugation with neuron-targeting IKVAV ligand, the membrane selective binds PC12 cells with zero binding to the control NIH3T3 cells. In summary, we synthesized a variety of monomers which provide the target functions and modulate material properties. We also developed several methodologies to control the nano-assembly process during polymerization. With the ability to control molecular structure and nanostructures, we demonstrated the applications of these materials in cell capturing and engineering.

Resume : Capture and isolation of circulating tumor cells (CTC) hold a great potential in cancer diagnosis, prognosis and personalized therapy, and tons of efforts have been carried out in recent years1. Most of the previous cell-capture platforms have a very high capture efficiency, but suffering from poor capture selectivity due to the presence of nonspecific interaction. In this study, to ensure both efficiency and selectivity at cell-capture, we fabricated a 3-dimensional conducting platform, which consists of a membrane mimicking PEDOT substrate2 and low density of membrane mimicking polymer chains grown from the conducting substrate. Its membrane mimicking feature promises the high selectivity of this conducting platform due to the absence of nonspecific interaction. Furthermore, the low density of cell-capture chains combines the softness and high density of accessible antibodies to ensure the high efficiency at cell-capture. The 3D conducting platform successfully demonstrated its superior performance at capturing CTCs than the previous nanodot PEDOT system3. We are now utilizing it as an electrochemical sensor to detect CTCs, and wish to report it in the near future. Reference 1. Li, Y. Q.; Chandran, B. K.; Lim, C. T.; Chen, X., Rational Design of Materials Interface for Efficient Capture of Circulating Tumor Cells. Adv Sci (Weinh) 2015, 2 (11), 1500118. 2. Zhu, B.; Luo, S. C.; Zhao, H.; Lin, H. A.; Sekine, J.; Nakao, A.; Chen, C.; Yamashita, Y.; Yu, H. H., Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer. Nat Commun 2014, 5, 4523. 3. Sekine, J.; Luo, S. C.; Wang, S.; Zhu, B.; Tseng, H. R.; Yu, H. h., Functionalized conducting polymer nanodots for enhanced cell capturing: the synergistic effect of capture agents and nanostructures. Advanced materials 2011, 23 (41), 4788-4792.

Resume : The local drug delivery by implanted devices or materials is an effective approach to manage chronic diseases. The electro-responsive platform supplies not only a chance to load a spatial-, temporal- and dosage-control on drug delivery, but also a potential to realize the on-demand delivery by a portable electric stimulus, which is particularly critical when a emergent medication become necessary. However, the electro-responsive delivery systems are challenged by the slow delivery rate, the poor reproducibility of drug release between the ON/OFF stimulation, and the PH variation during delivery. Toward solving these critical issues, we fabricated a reversibly electro-switchable drug delivery system based on electro-responsive PEDOT Materials. It complexes with functional molecules under reduction, while releases them quickly via applying a small value of oxidation potential. As the electro-switch is reversible, we could reload the drug molecules into the depot by applying a small reduction potential. We further demonstrated the release of molecules could be tuned precisely from a stable controlled rate to a burst release.

Resume : Almost all tissues in the body possess a complex internal and highly branched vascular systems, and the main function of vascular networks aim to simultaneously provide appropriate provision of oxygen and nutrients to cells while allowing more efficient exchange of metabolites during the blood perfusion. [1] Mimicking natural micro-vascular networks to keep long-term survival of engineered tissues in vitro and in vivo is still a key challenge in tissue engineering.[2] Here, we present a strategy to create biodegradable patterned artificial vascular scaffold (PAVSs) with a long-range functional transport system via 3D printing technologies. The process is general and versatile, can fabricate flexible PAVSs using various elastic biomaterials. The PAVSs are similar to natural vascular networks in different length scales with well-organized structural features. The branching microchannels are interconnected that can support physiologically relevant perfusion and also can be extended to perfusable microcirculation for mass transfer in three dimensions. An abundance of honeycomb pores are uniformly distributed in vascular walls to allow osmotic exchange of biomolecules. On the basis of this methodology, the PAVSs showed good scalability to create a series of composite scaffolds with built-in hierarchical transport system by incorporating with traditional tissue engineering scaffold manufacturing techniques. We demonstrate the power of PAVS to promote mass exchange in thick tissue by showing that the PAVS can maintain the metabolic functions and viability of viable heart cells for 5 days in vitro three-dimensional cell culture at high cell densities, and facilitate the angiogenesis extending from the host tissue for 8 weeks in vivo. [1] Kang HW, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol 2016. [2] Zhang B, Montgomery M, Chamberlain MD, Ogawa S, Korolj A, Pahnke A, et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat Mater 2016.

Resume : we report glucose oxidase-mimicking magnetic nanochains-supported AuNPs which can self-mix in small reaction volume, and easily be separated and recycled by using high saturation magnetization. Firstly, Fe3O4/PS-based magnetic nanochains were prepared by aligning them together in presence of an external magnetic field, and covalently linking the closely Fe3O4/PS NPs by self-polymerization of dopamine to form the polydopamine coated magnetic nanochains. Furthermover, the magnetic nanochains reduce HAuCl4 to prepare small AuNPs loaded on the surface of PMNCs. The naked AuNPs on the surface of magnetic nanochains exhibit GOx-mimicking catalytic activity. Therefore, magnetic nanochains@AuNPs are able to catalyze the oxidation of glucose in presence of oxygen producing gluconate and hydrogen peroxide, which are interrogated by HRP and TMB-based colorimetric assay. Moreover, both magnetic nanochains and magnetic nanochains@AuNPs could readily undergo magnetic separation, hence easily recyclable, and also can self-stir under a spinning magnetic field, which represent a platform for ultrasmall and self-stir GOx-mimicking magnetic nanochains@AuNPs biosensor for biomolecule recognition and label-free colorimetric detection.

Resume : Enzymes are macromolecular biological catalysts in living organisms, which can catalyze a wide variety of biochemical reactions with high activity and specificity. Inspired by natural enzymes, tremendous research efforts have been devoted to the development of artificial enzymes to mimic the functions of natural enzymes. Here, we prepare freestanding ultrathin two-dimensional (2D) metalloporphyrin-based metal-organic framework (MOF) nanosheets with thickness of sub-10 nm by a facile surfactant-assisted bottom-up synthetic method, which act as peroxidase mimic. In addition, in order to mimic the multiple functions of natural system, the hybrid nanosheets, i.e. growth of ultrasmall Au nanoparticles (NPs) on 2D MOF nanosheets, are designed and prepared. The obtained hybrid nanosheets, with glucose oxidase GOx-like and peroxidase-like activities, are used to mimic the natural enzymes and catalyze the cascade reactions, which are commonly completed by the oxidase-peroxidase coupled enzyme systems. Our study paves a new avenue to design nanomaterial-based biomimetic catalysts for mimicking natural system.

Resume : Flexible piezoresistive sensors (FPS) that can conform to curved surface or even human skin and bones extent the applications of conventional rigid pressure sensors to a much broader spectrum of biomedical disciplines, such as human-machine interaction, physiological signals monitoring, artificial knee implants, and clinical surgery. For some of these applications, e.g., artificial knee implants, it is particularly important for the sensor to provide a stable and repeatable pressure reading under bending. In this talk I will present our recent achievement in developing bending applicable sensors. In order to separately tune the mechanical and electrical properties of the sensor, we proposed a new graphene - polydimethylsiloxane (PDMS) hollow structure composite. Such design allows us to optimize the sensor sensitivity and linearity by tuning the number of graphene layers and hardness of PDMS, respectively. Furthermore, the “bending applicable” feature was achieved by controlling the pore density and thickness of the composite films. By reducing the film thickness to below 0.3mm and then optimizing the number of pore per inch (PPI), we achieved a low measurement error of <6% under various bending radius within the -25mm to +25mm range. The mechanisms underlying these observations were explained. Finally, we demonstrate the use of the sensor in epidermal pulse measurement and monitoring of robotic hand operation.

Resume : Bioelectronic devices have potential diagnostic and therapeutic applications in diverse medical fields such as the bionic ear and brain-computer interface. Electrode between the biotic and abiotic worlds has been demonstrated to be the most important part of these devices. However, implanting electrode inside the nervous system often incurs inflammatory response, which will lead to fibrous encapsulation, cutting off the connection between electrodes and electro-active cells and increasing the electrical impedance of the bioelectronics interface. Consequently, there is a high expectation for electrode coating of low impedance, high selectivity, high resolution and long-term stability. In early research, we have successfully developed a biomimetic conducting polymer film to facilitate a selective interaction to neural cells.1 However, the recording site is not the only part of an implanted electrode. The Insulating layer occupies the most part of the electrode, which plays very important role in the biocompatibility of the whole electrode. Therefore, we synthesized a protein/cell resistant poly(p-xylylene) thin film for the dielectric barrier. The design of bionic insulation significantly reduces the nonspecific adhesion of proteins/cells. We further integrated the biomimetic PEDOT derivatives with the bionic insulating material to fabricate an electrode array of all biomimicking polymers. We demonstrated that the feature of all biomimicking design ensures not noly a excellent proteins/cells resistance for the whole electrode but also a selective electrical interfacing of recording sites to neural cells. Reference: 1. B. Zhu, S.-C. Luo, H. Zhao, H.-A. Lin, J. Sekine, A. Nakao, C. Chen, Y. Yamashita and H.-h. Yu, Nature communications, 2014, 5.

Resume : Live cells are the basic working units in the biological tissue, performing different functions as natures’ microreactor. Assembly of sub-compartmentalized microreactors has become an important approach to mimic cells due to the structure similarity, ease of encapsulation of different subunits with multiple cargos, and the controllable activity initiation. With the aim to make artificial hepatocytes, we designed different sized microreactors with entrapped enzyme loaded liposomal subunits using droplet microfluidic or the layer-by-layer assembling technique. First, the synthetic partner particles or capsules were co-cultured with biological hepatocytes and successfully incorporated into the growing cell culture, forming bionic tissue with artificial and biological components. The surfaces of the particles or capsules coated with different polymers facilitated a beneficial biological response, i.e., the integration of the artificial and biological hepatocytes in a co-cultured tissue sheet as well as co-cultured cell tissue spheroids. The biological hepatocytes proliferation in the bionic tissue was assessed. Furthermore, detoxification, a key function of liver cells, was performed by loading the enzyme catalase, which can remove the cytotoxic compound hydrogen peroxide (H2O2), into the liposomal subunits of the artificial hepatocytes. The viability of hepatocytes in the bionic tissue was improved in the presence of active microreactors. These findings are a major step towards the beneficial combination of biological and synthetics entities with potential impact in regenerative medicine. Key words: cell mimicry, sub-compartmentalized microreactor, hepatocytes, detoxification, bionic tissue

Resume : Magnesium-based materials are preferential candidates for orthopedic implants due to their biodegradability, mechanical properties, and intrinsic antibacterial properties. However, the fundamental mechanism of bacteria killing remains unclear. In this study, a systematic study of the antibacterial properties of two common Mg-based materials is performed using a biofilm forming bacterium. Complete annihilation of the initial 3×10^4 bacteria is achieved with both materials in 0.1 mL LB medium in 24 h, whereas in the control they proliferate to 2-3×10^10. The bacteria are killed more effectively in the solution than on the surface, and the bacteria killing efficiency depends more on the concentrations of the magnesium ions and hydroxyl ions than the corrosion rate. The killing process is reproduced using formula solutions and killing is revealed to stem from the synergetic effects of alkalinity and magnesium ions instead of either one of them or Mg(OH)2 precipitate. Besides, reactive oxygen species (ROS) are detected from the bacteria during the killing process, but not likely produced by the redox reaction directly, because they are detected at least 3 h after the reaction has commenced. The average cell size increases during the killing process suggesting that the bacteria have difficulty with normal division, which also contributes to the reduced bacteria population. This systemetic study of antibacterial mechanism can give insight into better utilising magnisium-based biomaterials.

Resume : A smart contact lens, envisioned to correct or improve the vision, entails the integration of several electronics components such as: Si chips, a power source and an electro-optic module. All of them being interconnected by non-conventional electrical layouts in a fully stretchable platform. Such a platform must be designed with strict geometrical requirements and material limitations, to attain compulsory characteristics such as: biocompatibility, oxygen/light transparency, and being imperceptible by the human eye. The fabrication presented here relies on a planar process in order to later transform the flat platform (including thin film electronics circuitry, Si chips and interconnections) into a curvilinear spherical geometry by means of thermoforming. In particular, we introduce the platform’s mechanical carrier as a soft and biocompatible thermoplastic polyurethane (TPU), which serves as the thermoforming element and provides the essential support and stretchability. The latter enables the necessary conformability with the outer contact lens materials (i.e. based on hydrogels) and the spherical shape of the eye at the cornea. Furthermore, thanks to a developed thermoforming 3D and time domain Finite Element Model (FEM), the prediction of the final lens curvature and the analysis of the induced mechanical stress throughout the thermoforming step were attained. The model, based on the Generalized Maxwell viscoelastic model, was experimentally validated for several thermoforming temperatures (i.e. from 80°C to 140°C) and for 100 μm thick thermoplastic polyurethane (TPU) films. These films were patterned with optimized meandered designs in order to accommodate mechanical deformations during thermoforming. Such designs generated buckle-free platforms by reducing the hoop strain especially at its outer edge, which directly increased their mechanical robustness. Finally, the complete stack including the TPU carrier, a Si chip and a thin film flexible circuitry (i.e. stack of polyimde/gold/polyimide patterned by photolithography) was successfully thermoformed with a final curvature of 9 mm (12% difference with respect to the mold’s curvature of 8 mm). The independent and parallel processing of the thin film electronics and TPU carrier which are joined only at the end of the process, considerably increases their fabrication yield and decouples their processing incompatibilities. This, in combination with a short thermoforming step at relatively low temperature, paves the way towards mass scalable fabrication of soft smart contact lenses with integrated electronic components, including Si/foil-based chips, electro-optics, RFID antennas, micro-size batteries and photovoltaic cells, among others.

Resume : Titania doped with noble metal nanoparticles exhibits enhanced photocatalytic killing of bacteria under light illumination due to the localized surface plasmon resonance (LSPR) property. Recently, it has been reported that doping with Au or Ag can also endow TiO2 with antibacterial ability in the absence of light. However, the underlying mechanism is still far from understood. In this work, the antibacterial mechanism of Au-doped TiO2 nanotubes (Au@TiO2-NT) in the dark environment is studied and a novel EET from the aerobic S. aureus to the Au@TiO2-NT surface is discovered, which forms a ?bacteria-current? similar to the photocurrent on the electrochemical workstation. Electron-light region in the bacteria structure is also observed under transmission electron microscopy (TEM), supporting the EET phenomena mentioned above. The physiological changes in intracellular components leakage and ROS production are also studied to investigate the detailed bacterial killing process. Our results indicate that although the EET-induced bacteria current is similar to the LSPR-related photocurrent, the former takes place without light and no reactive oxygen species (ROS) are produced during the process. The EET is also different from what are commonly attributed to microbial fuel cells (MFC) because it is dominated mainly by the materials surface, but not the bacteria, and the environment is aerobic. EET on the Au@TiO2-NT surface kills Staphylococcus aureus but if it is combined with special MFC bacteria, the efficiency of MFC may be improved significantly.

Resume : Antifouling modification technology is developed for many biomedical applications such as blood-contact devices and biosensors. In this work, a photo-reactive polymer containing zwitterionic carboxybetaine groups was prepared by copolymerization of two kinds of methacrylic acids with carboxybetaine and azidoaniline. The carboxybetaine moiety is for low fouling and the azidophenyl moiety is for photo-crosslinking. The synthesized copolymers were coated onto polymeric substrates, and then covalently immobilized on the substrates by exposure to UV radiation. The poly(CBMA-co-AzMA) coating revealed that cell and platelet adhesion and protein adsorption to the substrates were reduced significantly compared to the untreated substrate. Furthermore, the direct immobilization of galactrosamine was carried out on the polymer coating by EDC/NHS chemistry. The galactose-immobilized surface had the potential for selecting hepatocyte adhesion from co-population of differing cell types. In addition, the incorporation of photolithographic technology could make micropatterns of poly(CBMA-co-AzMA) coating for cell co-culture of hepatocytes and fibroblasts. This work demonstrates that the reported technique is an economic and facile tool for layers of reduced adsorption of protein modification with functional groups in one step.

Resume : The versatility of carbon-based nanomaterials in terms of structural and electronic properties renders them broadly applicable electroactive components for future energy devices. Throughout the past decades, the fundamental basis has been laid for understanding and tailoring the charge-transfer characteristics of carbon nanomaterials ranging from fullerenes and carbon nanotubes to graphene, as well as chemically modified derivatives. Fullerenes are essential for understanding unidirectional charge-transport and -transfer phenomena at the molecular level, whereas with carbon nanotubes and graphene, efficient intrinsic bidirectional transport and transfer are realized. Such a plethora of nanomaterials fosters the idea of developing functional all-carbon-based devices. In this presentation, we survey the role of carbon-based nanomaterials in energy-conversion schemes. In particular, we highlight charge-transfer processes on the molecular scale in sp2 carbon in zero dimensions (fullerenes), sp2 carbon in one dimension (carbon nanotubes), sp2 carbon in two dimensions (graphene), and sp2/sp3 carbon in zero and two dimensions (defectuous carbon nanostructures).

Resume : We report on the thermal, electrical, and mechanical properties of alginate biopolymer nanocomposites prepared by solution casting with various amounts of montmorillonite clay (MMT), graphene oxide (GO) or reduced GO (rGO). Our data shows that the thermal stability of alginate nanocomposites can be improved by the introduction of cross-linking through divalent metal cations, albeit that under these conditions little influence by the amount of rGO remains. On the other hand, the electrical conductivity of divalent metal ion cross-linked-rGO improves approximately 10 orders of magnitude with increasing weight fraction of rGO, whereas it declines for sodium alginate-GO composites. In addition, storage moduli and glass to rubber transition temperatures show strong composition dependence as a consequence of complex interactions of the ions with both the polymer and the filler. We propose a mechanical model that allows for the accurate prediction of reinforcement by GO sheets in sodium alginate-GO composites taking into account the orientational order of the sheets. Creep tests reveal the complex nature of multiple stress relaxation mechanisms in the nanocomposites although the stretched exponential Burgers' model accurately describes short time creep compliance. References: [1] "Tunable Order in Alginate/Graphene Biopolymer Nanocomposites" K. Vilcinskas, B. Norder, K. Goubitz, F.M. Mulder, G.J.M. Koper, S.J. Picken, Macromolecules 2015, 48(22), 8323-8330. [2] ?Water Sorption and Diffusion in (Reduced) Graphene Oxide-Alginate Biopolymer Nanocomposites? Water Sorption and Diffusion in (Reduced) Graphene Oxide-Alginate Biopolymer Nanocomposites?, K. Vilcinskas, J. Zlopasa, K.M.B. Jansen, F.M. Mulder, S.J. Picken, G.J.M. Koper, Macromolecular Materials and Engineering (2016), 301(9), DOI: 10.1002/mame.201600154 [3] ?Composition dependent properties of graphene (oxide)-alginate biopolymer nanocomposites?, K. Vilcinskas, K.M.B. Jansen, F.M. Mulder, S.J. Picken, G.J.M. Koper, Polymer Composites (2016) DOI:10.1002/pc.24223

Resume : One important aspect of modern chemistry is directed towards the synthesis of complex nanomolecules that exhibit specific properties for applications in materials science and biology. However, the preparation of complex nanostructures combining the required functional groups remains often difficult and requires a large number of synthetic steps thus limiting both their accessibility and applicability. Our research group has shown that the preparation of easily accessible nanoscaffolds allowing for the grafting of one or more molecular entities is an appealing strategy to generate sophisticated nanomolecules. Overall, one of our main concerns is to increase the complexity of the molecular structures without increasing the synthetic difficulties. Our latest advances in this particular field will be presented with special emphasis on the preparation of bioactive compounds.

Resume : Nitrogen-doped multi-walled carbon nanotubes (N-MWCNTs) were decorated with metal nanoparticles (Rh, Pd, Ir, Pt, Au) and applied for simultaneous analysis of ascorbic acid (AA), dopamine (DA), and uric acid (UA) [1]. In N-MWCNTs/MNPs composite films three well-separated (not overlapped) oxidation waves were obtained for AA, DA, and UA analytes permitting their simultaneous analysis. Slight dependence of separation between oxidation waves of studied biomolecules on type of nanoparticles used for modification of N-MWCNTs was observed. Consequently, within the MNPs studied, AuNPs appear to improve better the electrocatalytic activity and sensitivity of N-MWCNTs. Namely, on N-MWCNTs/AuNPs the oxidation overpotential of AA decreases significantly and well-separated oxidation waves for interfering AA and DA compounds can be obtained. In addition, on N-MWCNTs/AuNPs well-separated oxidation waves for DA and UA can be observed. Consequently, the detection ability of N-MWCNTs/AuNPs towards simultaneous oxidation of AA, DA, and UA appears to be greater compared to other composite films [2]. References 1- N.G. Tsierkezos, P. Szroeder, U. Ritter, Microchim. Acta (2014) 181, 329-337. 2- N.G. Tsierkezos, U. Ritter, Y. Nugraha Thaha, C. Downing, P. Szroeder, P. Scharff, Microchim. Acta (2016) 183, 35-47.

Resume : The scientific interest in diamond surface started already in 1970s for its field emission properties originated from negative electron affinity. Since 1990s due to the development in boron doping in CVD process, diamond has been investigated as one of the most promising electrode materials for analytical chemistry because of its unique electrochemical properties including outstanding stability, wide electrochemical window, flexible surface termination and abundance of surface chemistry. In the last ten years, with the advance in diamond dry- etching and templated growth technology, surface-enlarged, nanostructured diamond electrodes are now widely available. For example, using self-organized Ni nanoparticle as etching mask, vertically aligned diamond nanowires can be fabricated; using quartz or glass fiber paper as growth templates, porous diamond membranes are fabricated [1, 2]. These progresses have brought about new applications in energy related topics and membrane technology. In our previous work, these diamond-based materials has been successfully applied in double layer capacitor, as well as the current-collecting material [3] for pseudocapacitive/battery materials [4]. In these applications, diamond showed interesting properties which differs from traditional sp2 carbon materials. In our recent progress, we have demonstrated the ability of diamond membrane in electrochemical separation processes. Compared to polymer membranes or membranes based on sp2 carbons, diamond membranes can survive in aggressive media and high temperature conditions. Also, the ion selectivity can be controlled by surface terminations as well as the bias potential of the membrane. Therefore, this kind of membranes is very promising for the electrochemical separation processes such as desalination, pollutants concentration and protein separation. However, both the fabrication and application of diamond membranes are so far reported only in very limited cases. In this paper, we focus on our recent development with respect to the templated diamond growth using quartz fiber filter as the growth template [5]. With optimized microwave CVD growth, nanocrystalline diamond film is fully coated onto the quartz fiber as has been confirmed via SEM. The diamond quality is evaluated via Raman spectroscopy. The potential window of the diamond membrane is determined to be over 3 V in aqueous electrolyte solutions. By applying potential to the membrane, reactive ions will accumulate inside the membrane and change its porosity. As a result, the ion flux through the membrane can be well tuned. This ion selectivity can be used to separate charged molecules. Moreover, due to the chemical stability of diamond, the membrane can be cleaned in situ via a high potential Therefore, this membrane is also suitable for applications where only simple in-situ maintenances are possible. This project has received funding from the European Union's Horizon 2020 Programme under Grant Agreement no. 665085 (DIACAT). [1] F. Gao*, M. T. Wolfer, C. E. Nebel. Highly porous diamond foam as a thin-film micro-supercapacitor material, Carbon, 2014;80:833-840. [2] F. Gao*, G. Lewes-Malandrakis, M. T. Wolfer, W. Müller-Sebert, P. Gentile, D. Aradilla, T. Schubert, C. E. Nebel, Diamond-coated silicon wires for supercapacitor applications in ionic liquids, Diamond and Related Materials, 2015; 51:1-6. [3] F. Gao*, C. E. Nebel, Diamond-Based Supercapacitors: Realization and Properties, ACS applied materials & interfaces, 2016; 8 (42): 28244–28254 [4] F. Gao*, C. E. Nebel, Diamond Nanowire Forest Decorated with Nickel Hydroxide as a Pseudocapacitive Material for Fast Charging-Discharging, Physica Status Solidi (a), 2015; 212(11): 2533-2538 [5] F. Gao*, C. E. Nebel, Electrically Conductive Diamond Membrane for Electrochemical Separation Processes, ACS applied materials & interfaces, 2016; 8 (28): 18640–18646

Resume : Buckminsterfullerene and its soluble derivatives possess a unique set of electronic properties, most notably a high electron affinity and electron mobility. This talk will discuss how the use of fullerenes can benefit two (renewable) energy technologies: (1) polymer solar cells and (2) power cables. Polymer solar cells attract considerable attention as a potential renewable energy technology. The light-harvesting efficiency of polymer solar cells based on conjugated polymer:fullerene blends is continuously increasing. However, before practical applications can be considered, the long-term thermal stability of these devices must be improved. I will introduce two tools based on (1) nucleating agents and (2) fullerene mixtures, which permit to considerably enhance the thermal stability of this promising class of materials. Power cables are essential for grid integration of renewable energy installations, which are often located in sparsely populated areas. I will discuss the use of fullerenes as voltage-stabilizers for polyethylene, i.e. additives that increase the dielectric strength of an insulation material, which is facilitated by the high electron affinity of fullerenes. The use of such additives may considerably reduce power transmission losses and thus enhance the scope of renewable energy technologies such as solar cells.

Resume : Graphene offers promising advantages for biomedical applications. However, adoption of graphene technology in biomedicine also poses important challenges in terms of understanding cell responses, cellular uptake or the intracellular fate of soluble graphene derivatives. In the biological microenvironment graphene nanosheets might interact with exposed cellular and subcellular structures resulting in unexpected regulation of sophisticated biological signaling. More broadly, biomedical devices based on the design of these 2D planar nanostructures for interventions in the central nervous system (CNS) requires an accurate understanding of their interactions with the neuronal milieu. Here, we describe the ability of graphene oxide nanosheets to down-regulate neuronal signaling without affecting cell viability. Beyond the safe design of nanomaterials, such a specific interference affecting exquisite CNS signaling may offer possibilities in neuropharmacology, when specific targeting of excitatory synapses is desired. The use of nanoparticles as therapeutics is in fact fueled by their ability to circumvent biological barriers and targeting of synapses has created the basis for theranostics applications. Our observations with thin s-GO flakes illustrate the potential of 2D nanosheet physical properties to engineer specific glutamate-transmission modulators.

Resume : Semiconducting single-walled carbon nanotubes (s-SWCNTs) are potentially good candidates for in vivo optical imaging because they fluoresce in short-wave infrared (SWIR; 900-1600 nm) region. This provides lower scattering and autofluorescence backgrounds than in the visible range. The richness of their structural diversity provides a wide variety of SWIR emission wavelengths, enabling many applications including strain sensing, spectrally multiplexed immunoprobing, and spectral triangulation. Not only does the emission of SWCNTs expand the immunoprobe detection window beyond visible wavelengths into the SWIR, but it also provides spectral multiplexing because of the sharp and distinct emission peaks of different SWCNT structural species. However, the optical detection of nanomaterials is hampered by the strong absorption and scattering of light in tissues. Fortunately, the emission of SWCNTs located at the long-wavelength edge of the optical window, which has the optimal light transparency in tissues. The relatively high transparency and low backgrounds yield high contrast for in vivo detection. Recent advances of in vivo SWCNT imaging have demonstrated the viability of using SWCNTs as immunoprobes, but more sensitive detection with lower detection limits is desired. Also, three dimensional localization of SWCNTs in vivo instead of two dimensional imaging is another emerging challenge. We have therefore been developing sensitive in vivo detection, using a unique InGaAs avalanche photodiode detector, combined with a new spectral triangulation method with sub-millimeter resolution for locating SWCNT-immunoprobes targeted to cancer cell markers. We hope that our recent studies will advance the trace detection and localization of SWIR-fluorescent nanomaterials in preclinical research.

Resume : Multi-shell fullerenes, also known as carbon nano-onions (CNOs) are structured by concentric shells of carbon atoms and display several unique properties, such as a large surface area to volume ratio, low density and a graphitic multilayer morphology.1 In my research group we have developed a versatile and robust approach for the functionalisation of CNOs, involving the facile introduction of a number of simple functionalities onto their surface. Multimodal imaging probes based on carbon nano-onions (CNOs) have emerged as a platform for bioimaging because of their cell-penetration properties and minimal systemic toxicity.2-3 We have developed a synthetic multi-functionalisation strategy for the introduction of different functionalities (receptor targeting unit and imaging unit) onto the surface of the CNOs The modified CNOs display high brightness and photostability in aqueous solutions and their selective and rapid uptake in two different cancer cell lines without significant cytotoxicity is demonstrated. The localization of the functionalized CNOs in late-endosomes cell compartments is revealed by a correlative approach with confocal and transmission electron microscopy.4 Understanding the biological response of functionalized CNOs with the capability to target cancer cells and localize the nanoparticles in the cellular environment, will pave the way for the development of a new generation of imaging probes for future biomedical studies. References: 1. J. Bartelmess and S. Giordani Beilstein J. Nanotechnol. 2014, 5, 1980–1998. 2. M. Yang, K. Flavin, I. Kopf, G. Radics, G. J. McManus, B. Moran, L. Echegoyen, S. Giordani and E.C. Lavelle Small 2013, 9, 4194-4206. 3. M. d’Amora, M. Rodio, J. Bartelmess, G. Sancataldo, R. Brescia, F. Cella Zanacchi, A. Diaspro and S. Giordani Scientific Reports, 2016 6, 33923 4. M. Frasconi, R. Marotta, L.Markey, K. Flavin, V. Spampinato, G. Ceccone, L. Echegoyen, E. Scanlan and S. Giordani Chem. Eur J. 2015, 21, 1971-19080. Acknowledgments: COST Action CA 15107 “Multi-Functional Nano-Carbon Composite Materials Network (MultiComp)”

Resume : The network medicine concept has produced a major paradigm shift in the way we understand and treat disease. Based on molecular profiles, symptoms-unrelated diseases could be grouped in specific “diseaseome” clusters. One example is the “redox diseaseome” that is encompassing diseases underlined by chronic low-grade oxidative stress, such as cancer, diabetes, cardiovascular and neurodegenerative disorders. Nanomaterials have arisen lately as valuable vehicles for therapeutic molecules. For improving the efficacy of nano-enabled therapies, the properties and consequent biological effects of nanostructures should be smartly tailored to target the pathologic molecular profile of disease and patient. The case of carbon and iron oxide nanostructures designed as vehicles for the treatment of redox diseases will be discussed in terms of impact on oxidative stress, redox signaling and antioxidant response. A special focus will be given to the Janus face of reactive oxygen species which may act as friends or foes, depending on the context. Acknowledgements: COST Action CA15107 “Multi-Functional Nano-Carbon Composite Materials Network (MultiComp)”, M-Era.Net project 52/2016 (NANOTHER)

Resume : Carbon nano-onions (CNOs) are a class of carbon nanomaterials which presents high cellular uptake, low cytotoxicity and weak inflammatory potential [1]. In particular, boron dipyrromethene (BODIPY) functionalized CNOs are suitable for high resolution imaging [2]. In this study, we focus our attention on the possible adverse effects and biocompatibility of BODIPY CNOs on the development of zebrafish (Danio rerio). This is an excellent and predictive vertebrate model organism for addressing toxicity of numerous nanomaterials at the whole animal level [3]. We characterize all the macroscopic effects by assessing different exposure periods and end-points, such as possible presence of malformations and behavioral anomalies. Furthermore, we carry out a 3D mapping of BODIPY CNOs in the whole zebrafish embryo/larvae by means of advanced fluorescence microscopy techniques, such as inverted selective plane illumination microscopy (iSPIM). These techniques provide a good optical section capability, low photo damage and fast imaging speed, allowing to 3D imaging of zebrafish embryos and larvae [4]. As the use of carbon based materials constantly increases, our results will open new perspectives in the biosafety of carbon nanomaterials. [1] M. Yang, K. Flavin, I. Kopf, G. Radics, C.H. A. Hearnden, G.J. McManus, A. Villalta-Cerdas, L.A. Echegoyen, S. Giordani, E.C. Lavelle "Chemical surface functionalization of carbon nanoparticles modulates inflammatory cell recruitment and NLRP3 inflammasome activation", Small, 9, 4194-4206 (2013). [2] J. Bartelmess, E. De Luca, A. Signorelli, M. Baldrighi, M. Becce, R. Brescia, V. Nardone, E. Parisini, L. Echegoyen, P.P. Pompa, S. Giordani "Boron dipyrromethene (BODIPY) functionalized carbon nano-onions for high resolution cellular imaging", Nanoscale, 6, 13761-13769 (2014). [3] M. d'Amora, J. Bartelmess, G. Sancataldo, F. Cella Zanacchi, A. Diaspro, S. Giordani "Biocompatibility and biodistribution of functionalized carbon nano-onions (f-CNOs) in a vertebrate model, Scientific Reports, 6, 33923 (2016). [4] Z. Lavagnino, G. Sancataldo, M. d?Amora, P. Follert, D. De Pietri Tonelli, A. Diaspro, F. Cella Zanacchi "4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM) ", Scientific reports, 6, 23923 (2016). ACKNOWLEDGEMENTS: Cost action CA15107 "Multi-functional nano-carbon composite materials network"

Resume : Multi-shell fullerenes, known as carbon nano-onions (CNOs), have recently aroused great interest among researchers and have been successfully applied in a variety of different fields of application [1]. CNOs are attractive platforms for imaging, diagnostic and therapeutic applications, as they are small and they can be surface chemically modified allowing cell penetration and cell recognition respectively. In particular, the development of novel fluorescent systems for bio-imaging applications is a research field of increasing interest. One of the strategy to enhance bio-imaging rely on the development of imaging probes for the biologically relevant near-infra red (NIR) and far-red region, where tissue exhibit minimal absorbance[2]. Our recent reports showed that fluorescently labelled CNOs exhibit weak inflammatory potential and a low cytotoxicity[3]. They are readily internalized by cancer cells and deposited in the lysosomes[4, 5]. Moreover, in vivo studies on zebrafish (Danio Rerio) during the development shown their biocompatibility and homogenous distribution in a vertebrate model system, making them suitable as biomedical probes[6]. However the potential of carbon-based nanomaterial for biological application can be further enhanced by increasing their solubility in water-based medium obtaining small specialized nanoparticles with a narrow size distribution. Here we report the development of a new generation of far-red imaging probe with a great dispersibility in biological media for biomedical applications. The fluorescent CNOs have been characterized by a variety of different analytical techniques such as thermogravimetric analysis (TGA), dynamic light scattering (DLS), zeta potential, spectroscopy (Raman, FT Infrared, Fluorescence) as well as microscopy. The internalization and cytotoxicity of the fluorescent labelled CNOs were analyzed in human cervical carcinoma (HeLa) and human breast cancer (MCF-7) cells. Our results demonstrated that both cell lines accumulated the functionalized CNOs without any significant toxic effect on cell morphology and cell viability, showing a similar behavior to the untreated control cells. Moreover, confocal imaging shown that the functionalized CNOs present a high fluorescence intensity and localized partially in the lysosomes. Our findings confirm the excellent potentialities of these functionalized carbon nanomaterials as biocompatible platform for high-resolution biological imaging. References: [1] Bartelmess, J. et al. Beilstein J. Nanotechnol. 2014, 5, 1980 [2] Giordani. et al. J. Mater. Chem. B 2014, 2, 2422 [3] Yang, M. et al. Small 2013, 9, 4194 [4] Bartelmess, J. et al. Nanoscale 2014, 6, 13761 [5] Frasconi, M. et al. Chem. Eur. J. 2015, 21, 19071 [6] d’Amora, M. et al. Scientific Reports 2016, 6, 33923 Acknowledgments: COST Action CA 15107 “Multi-Functional Nano-Carbon Composite Materials Network (MultiComp)”

Resume : Nanotubes and fullerene-like nanoparticles of WS2 and to some extent also MoS2 are produced now in large amounts and serve for numerous commercial applications, mostly as solid lubricants. The synthesis of different nanotubes from binary, ternary and even quaternary nanotubes has been advanced in recent years. In this short presentation some new studies involving individual WS2 nanotubes, like quasi-1D superconductivity, wetting and electromechanical resonators will be briefly described. In the second part of this talk new biomedical applications of the IF/INT will be briefly described. In particular lubrication of the entry/retrieval of medical devices, like catheters and laparoscopes by Re-doped IF nanoparticles; reduced encrustation of urological catheters and reinforcement of biocompatible polymers, like polyurethane, PVA and others will be discussed in light of new potential medical technologies.

Resume : The temporal and spatial control of the delivery of bioactive molecules is an essential aspect of many therapeutic solutions to direct and modify biological events such as wound healing or modulation of the immune system after implantation. The choice of the delivery platform is also crucial because cells need a specific microenvironment in vivo. The release is generally controlled in a passive manner either via diffusion rate of the bioactive agent or through the degradation rate of the delivery systems. So we have designed an ECM mimicking membrane loaded with dopamine based nanoparticles which can be functionalized with bioactive molecules. Our films are prepared by spin-coating and are composed of gelatin and tyraminated hyaluronic acid. Two enzymatic crosslinking are performed to obtain an interpenetrating network. Our results showed that a slow release profile can be maintained for long periods (several weeks) without any cytotoxic effect on human cells. Nanoparticle enrichment of release platforms provides a fine control over the diffusion and partition behavior of bioactive molecules which can be harnessed for establishing long term gradient for applications such as tissue engineering Key words: nanoparticles, dopamine, controlled release, gelatin, thin films

Resume : Cardiovascular diseases are the leading causes of high morbidity and mortality worldwide. Current therapies have still limited rate of success, therefore novel/modified nanomaterials are emerging as promising alternatives for the treatment of heart diseases. Our lab has shown that porous silicon-based nanoparticles (PSi NPs) are promising biocompatible nanovectors for drug delivery applications [1−4]. Thus, in this work, we have successfully modified PSi NPs with heart-homing peptides to improve the cytocompatibility of the particles in primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts, enhance their cellular uptake, and improve their accumulation in heart tissue in vivo in a myocardium infarcted (MI) rat model. The PSi NPs were modified with DOTA (D), heart-homing peptides (ANP, P2 and P3) were covalently conjugated to the NPs and, finally, the NPs were radiolabeled. In vitro studies evaluated the cellular viability and interactions. A MI rat model induced by isoprenaline injection was used to study the 111In labelled NPs after i.v. administration. The heart accumulation of the NPs was investigated by SPECT/CT. The safest concentrations of the NPs found in vitro were up to 50 µg/ml. Un-D-ANP NPs were internalized in higher amounts by primary cardiomyocytes, non-myocytes and H9c2 cardiomyoblasts. A competition assay demonstrated that Un-D-ANP NPs were internalized via the guanylate cyclase A receptor in primary cardiomyocytes. Enhanced accumulation of the NPs was observed for all peptide-modified nanosystems in heart up to 3-fold. References: [1] Liu et al., J. Control. Release (2013), 170: 268. [2] Correia et al, ACS Appl. Mater. Interfaces (2015), 7: 23197. [3] Tölli et al., Biomaterials (2014) 35: 8394. [4] Ferreira et al., Biomaterials (2016) 94: 93.

Resume : Theranostic Cytochrome c (Cyt c) is a mitochondrial protein involved in the intrinsic apoptotic pathway of cells. After Cyt c release into the cytosol, the caspase mediated apoptosis cascade is activated resulting in programmed cell death. This intrinsic property of Cyt c can be used to treat cancer. Herein, we explore the covalent immobilization of Cyt c into ordered mesoporous silica nanostructures for intracellular drug delivery of this theranostic cargo to colon cancer cells aiming at affording subsequent cell death. The targeted delivery of a functional apoptosis-initiating protein Cyt c to cancer cells, we formulated ordered silica nanostructures for the simultaneous encapsulation of cytochrome c and a cancer cell targeted aptamer AS1411 to colon cancer cells. The potential therapeutic property of these nanocargos was demonstrated by the induction of apoptosis upon intracellular delivery. The results clearly demonstrate that theranostic nanostructure upon formulation of a smart drug delivery system and upon delivery into cancer cells and highlight the general potential of this nanostructure in cancer therapy.

Resume : In the present study, a facile synthesis route was developed to prepare surface functionalized superparamagnetic Cobalt zinc ferrite (CZF) magnetic nanoparticles (MNPs) by using triethylene glycol (TEG) as reducing agent and surface modifier ligand. Initially structural, morphological, and magnetic characterization were carried out in order to confirm their size, poly dispersity, colloidal stability, and magnetic property. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of triethylene glycol (TEG) on the surface of CZF MNPs. The CZF MNPs are of superparamagnetic in nature with high saturation magnetization, good colloidal stability, high specific absorption rate (SAR), and excellent biocompatibility. All these properties are crucial, for their use as nanomedicine in cancer theranostics such as magnetic fluid hyperthermia (MFH) treatment; which is considered as one of the most promising cancer therapy. The prepared CZF MNPs are found biocompatible with MCF7 (human breast cancer) and L929 (mouse fibroblast) cell lines and Vero cell line (monkey kidney cell line), when tested by MTT and SRB assays. Cell particle interaction was studied in depth, by using multiple staining techniques combined with confocal microscopy. Finally, an In vitro hyperthermia experiment was carried on MCF7 cells, resulting in death of MCF7 cells up to 80% within 60 min. The research demonstrates that, the prepared CZF MNPs can be used as a potential candidate for effective MFH treatment for cancer cell death. Reference: 1. R.A. Bohara, N.D. Thorat, A.K. Chaurasia, S.H. Pawar, RSC Adv., 5, 47225 (2015) Corresponding Author: Raghvendra A Bohara

Resume : Surface layer proteins form regular 2-D crystalline arrays in the nanometer regime (S-layers) on solid substrates by self-assembling singular protein units that are cross-linked with calcium ions. An outstanding feature of S-layers is that their assembly and morphology can be electrochemically controlled and manipulated.[1-5] Moreover, S-layers can serve as biointerfaces that exhibit excellent antifouling properties.[6] The controlled orientation of S-layers for the formation of cytophobic and cytophilic recrystallized monolayers on glass supports has been reported recently.[7] In this study the influence of chaotropic and kosmotropic ions on the dynamics and the mechanism of the adsorption process of S-layer proteins of Lysinibacillus sphaericus CCM 2177 were investigated by electrochemical in situ techniques (EQCM, FT-IRRAS, AFM). [1] M. Handrea, M. Sahre, A. Neubauer, U.B. Sleytr, W. Kautek, Bioelectrochemistry 61 (2003) 1. [2] U.B. Sleytr, M. Sara, W. Kautek, EP 1 402 055 B1 (2007). [3] C. Zafiu, G. Trettenhahn, D. Pum, U.B. Sleytr, W. Kautek, Phys. Chem. Chem. Phys. 13 (2011) 3478. [4] C. Zafiu, G. Trettenhahn, D. Pum, U.B. Sleytr, W. Kautek, Phys. Chem. Chem. Phys. 13 (2011) 13232. [5] C. Zafiu, T. Werzer, G. Trettenhahn, D. Pum, U.B. Sleytr, W. Kautek, J. Phys. Chem. C 118 (2014) 29860. [6] M.M. Picher, S. Küpcü, C.-J. Huang, J. Dostalek, D. Pum, U.B. Sleytr, P. Ertl, Lab Chip 13 (2013) 1780 [7] M. Rothbauer, S. Küpcü, D. Sticker, U.B. Sleytr, P. Ertl, ACS Nano 7 (2013) 8020

Resume : Photothermal therapy (PTT) is a novel, non-invasive method for cancer treatment in which there is significant research interest in further developing. Effective PTT agents must be biocompatible, highly selective, stable and photosensitive. Its optical absorbance must be in the near infra-red region, which is capable of penetrating through biological tissue. To this end, this investigation aims to design and synthesise novel nanoparticles, combining a polymer core, a gold shell and a block copolymer coating, which would result in a highly tuneable PTT agent. To date, the only methods used to modify the optical properties of gold nanostars have been to alter their size and degree of branching, while no investigation has examined whether varying the refractive index of the core will have an impact. As such, in this investigation, multiple polymer cores, of varying refractive indices, will be synthesised and their effect on the optical properties of both gold nanospheres and nanostars will be analysed. In addition to this, an in-house synthesised amphiphilic copolymer will be used to coat the nanoparticles to increase stability, selectivity and biocompatibility for potential in vitro and in vivo studies. The optical properties and heating efficiencies of all nanoparticles created in this study will be compared. Keywords: theranostics; refractive index; amphiphilic copolymer

Resume : The development of intelligent stimuli responsive theranostic system that can detect and treat cancer at its early stage is an emerging area in the field of nanobiotechnology. Multiple imaging agents that combine, for example, magnetic resonance imaging (MRI) with optical imaging, can be used at the same time as a drug delivery agent. In this work mesoporous silica coated Gd based nanoparticles with enhanced biosafety were successfully prepared. Results showed that nanoparticles were homogeneous regarding chemical composition, silica layer thickness, total size and morphology. By simply varying the reaction parameters mesopore sizes, surface area and pore volume could be adjusted for enhanced adsorption and release of different anti-cancer drugs. This strategy will allow surpassing active cancer drugs poor specificity and dose-limiting toxicities during chemotherapy.

Resume : Magnetite (Fe3O4) is a favorite material to be used in biomedical applications owing to its remarkable magnetic properties and suitable biocompatibility & biodegradability. It has been widely studies as a material of choice for magnetic hyperthermia therapy, controlled drug delivery, magnetic separation and as a magnetic resonance imaging contrast agent [1-2]. Under an oscillating magnetic field magnetite nanoparticles generate heat due to Néel losses and Brownian rotations in physiological fluids [3]. Magnetite nanoparticles also respond to certain visible light wavelengths near infrared region and are excited upon irradiation. During de-excitation it releases extra energy into molecular vibration modes that transform into thermal energy [4]. Current study is about combining the magnetic hyperthermia and photothermal therapies into a single bimodal system for cancer therapy. The synthesized magnetite nanoparticles were superparamagnetic having appropriate colloidal stability due to being coated with polyethylene glycol. Cell viability and cytotoxicity were studied on HeLa cells using MTT assay and proteome apoptosis kit. They were subjected to an oscillating magnetic field of 375 kHz & 170 Oe for hyperthermia. For photothermal therapy, the system was irradiated with a laser emitting 808 nm wavelength which is a near infrared regime in electromagnetic spectrum. The two treatments were performed separately as well as in combination and the combined treatment was multifold more effective in treating the cancer cells as compared to separate sessions. References [1] K.M. Krishnan, IEEE Trans. Magn. 46, 2523 (2010). [2] S.A. Shah, K.M. Krishnan, et al., Phys. Rev. B, 92, 094438 (2015). [3] S.A. Shah, et al., Mater. Chem. Phys, 137, 365 (2012). [4] M. Chu, Y. Shao, et al., Biomaterials, 34, 4078 (2013).

Resume : Bare laser-synthesized Au and Si nanoparticles (AuNPs and SiNPs) gather exemplary physicochemical properties for advanced imaging and therapeutic modalities. Here, we explore the feasibility to functionalize electrospun hybrids nanofibers based-on chitosan(PEO) with bare-NPs, employed as additives for projected applications in tissue engineering. We report the possibility to graft bare-NPs on fiber surface via electrostatic interaction ensured between polycationic surface of nanofibers and negative charge surface of NPs, offering thus additional anchoring interaction sites with biological tissues. No interference was observed on chemical composition of chitosan(PEO) nanofibers. Moreover, the functionalization of nanofibers with bare-NPs leads to quite different diameter fibers, suggesting potential improvement of fiber surface reactivity. We also show, throughout thermal analyses that bare-NPs confer thermal stability at higher temperature and can be potentially explore for controlled drug release. Finally, biological properties of the nanofibers were assessed through preliminary viability tests conducted on HaCaT cells. After 24 h of incubation time, no adverse effects were observed confirming the biocombatibilty of the hybrides nanofibers. As first encouraging attempt, the proposed concept promises exciting perspectives in the development of innovative mutifunctional platforms gathering new properties for tissue engineering field.

Resume : Formation of biological materials is a well-controlled process by biomolecules especially by proteins. Proteins can control nucleation and mineralization of biomaterials, thereby forming the hard tissues of biological organism such as bones, teeth and shells. In this study design, implementation of multifunctional designer proteins is demonstrated for fluorescent silica micro/nanoparticles synthesis. R5 motif of silaffin polypeptide which is known for its silicification capability was fused genetically into three different fluorescent proteins with the intention of forming modified fluorescent proteins. R5 peptide domain served as a robust and cheaper purification tag for the proteins in addition to providing silica synthesis at ambient conditions. Three functional fusion constructs have been designed, including GFP-R5, YFP-R5 and mCherry-R5. R5 peptide tag was exploited to purify fluorescence proteins through silica gel resin and later synthesis of bioluminescent silica particles. Bio-enabled particles are found biocompatible for usage in novel biomedical and biomaterial applications.

Resume : The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technology. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepared by incubating 100 nm gold nanoparticles in a solution containing an optimized concentration of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphological semblance to natural viral particles under nanoparticle tracking analysis and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture.

Resume : Layered double hydroxide (Mg/Al-CO3-LDH) nanoparticles were synthesized by coprecipitation and utilized as a support for superoxide dismutase enzyme (SOD). Structural properties of the obtained materials were probed by X-ray diffraction experiments, several spectroscopic methods (UV-Vis, IR, fluorescence), TEM and SEM, while colloidal stability and electrophoretic properties were investigated by time-resolved dynamic light scattering and electrophoresis. At appropriate loading, SOD adsorbs quantitatively on the surface of LDH due to the electrostatic and hydrophobic interactions. Obtained material exhibited strong enzymatic activity with moderate resistance to salt induced aggregation. By coating this material with heparin, novel hybrid nanomaterial was obtained. Both processes, adsorption of SOD and coating by the biopolymer, were completely harmless to the 3D structure of the enzyme. Dispersion of this type of coated material exhibited excellent colloidal stability due to electrostatic and steric stabilisation. In addition, the nanocomposites showed significant SOD activity1. In summary, the designed hybrid nanomaterials are a suitable candidate for applications, wherever stable dispersions of antioxidant activity are required for instance in biomedical treatments or in chemical manufacturing processes. References : 1. Pavlovic M.; Rouster P.; Szilagyi I., Synthesis and formulation of functional bionanomaterials with superoxide dismutase activity. Nanoscale. 2017, 9, 369–379.

Resume : Regenerative electroless etching (ReEtching) is a method of producing nanostructured semiconductors in which an oxidant (Ox1) is capable of initiating etching by injecting holes into the semiconductor valence band and a second oxidant (Ox2), which would be unreactive in the primary reaction, is used to regenerate Ox1. Thereby the extent and the rate of reaction are controlled by the amount and rate of Ox2 added in the process. This general strategy is demonstrated specifically for the production of highly luminescent, porous Si from the reaction of V2O5 in HF(aq) as Ox1 and H2O2(aq) as Ox2 with Si powder, chunks and wafers. Numerous applications of nanostructured silicon, e.g. consumer products, nanomedicine and biosensing, would benefit from economical production of porous powder on the kilogram to ton scale. However, that has been infeasible up until now because of the uncontrollable electroless etching processes. The new ReEtching method overcomes the problem and may be used in an industrial level production of mesoporous silicon. In addition to a feasible large-scale production of different kind of nanostructured Si structures, ReEtching can also be used to pre-anodized mesoporous silicon powder. The result is stunningly bright and persistent photoluminescence due to much smaller quantum-confined structures within the mesopores produced by ReEtching, also enabling biosensing, diagnostic and even theranostic use of ReEtched particles.

Resume : Most synthetic plastics are derived from fossil resources and nondegradable. The increased use of plastics over the years has resulted in increases in waste that have become significant concerns because of their negative impacts on the environment. With the growing concerns towards the environment, many academic and industrial researchers are investigating to develop non-petroleum-based and sustainable feedstocks [1-2]. Recent advances in polymeric composite science offers significant opportunities for new, improved green materials from renewable resources that are optionally recyclable, biocompatible, and biodegradable, thereby enhancing global sustainability [3-4]. In that respect bio-based polymeric composites are attracting a great deal of attention because of the inherent advantages of these polymers such as biodegradability, low toxicity, easy availability, economy and the control of carbon dioxide emissions that lead to global warming. The goal of this study focuses on the improvement of Poly(hydroxybutyrate-co-valerate), PHBV properties so it can be effectively used for different applications as well as maintaining its biodegradability. PHBV, is a biodegradable polymer which is formed in bacterial cells as an energy reservoir. To achieve this goal, boron nitride was used to enhance polymer properties. Boron nitride (BN) is a ceramic material with attractive physical properties. Our results showed that the PHBV/BN nanocomposites exhibited promising improvement in various properties. Acknowledgements M. Öner thanks the Scientific and Technological Research Council of Turkey (TUBITAK, Project No. 215M355), and M.Bechelany thanks the Campus France (PHC Bosphore No.35211XD) for funding this work under a Bilateral Cooperation Program between Turkey and France. References 1. C. K. Williams and M. A. Hillmyer, Polym. Rev., 2008, 48, 1–10. 2. A. Shah, F. Hasan, A. Hameed and S. Ahmed, Biotechnol. Adv., 2008, 26, 246–265. 3. M. Öner, A. A. Çöl, C. Pochat-Bohatier and M. Bechelany, RSC Adv., 2016, 6, 90973–90981. 4. N. Tenn, N. Follain, J. Soulestin, R. Cretois, S. Bourbigot and S. Marais, J. Phys. Chem. C, 2013, 117(23), 12117–12135.

Resume : Learning how to modify of nanocarbon materials surface (nanotubes, fullerenes) by design bioactive surface is one of most challenging problems in functional biointerface nanoscience and nanotechnology. Meeting this challenge requires selection of individual modifed molecular components and artful control of how these molecules are arranged and interacted developing biosensing principles. Previous our investigation in the area of chemical modeling of surface modification of carbon nanotubes and fullerols with useful properties and coordination chemistry of transition metal azole complexes gave beginning for research in the field. We propose the new approach for modelling of surface modification of these nanocarbons by self-assembled supramolecular architectures based on azole complexes of transition metals, which are compatible with biomolecules. This model was confirms by UV-vis, IR spectroscopy, EPR and AFM investigation. Such modified nanocarbon surface by metal - azole complexes provided the necessary information to analyze the possibility use of new materials in biosensor systems. The next stage of the study supramolecules is photoexcitation complex with amino acids, which change the coordination environment of metal and the absorption spectra due to d - d transitions shifts. As a result, received experiments are confirmed of a "smart" supramolecule that recognizes protein amino acids.Asknowledgement: thanks Liliana Lukashuk as chemist for proposed models, supported experiments and discussions.

Resume : Dressings for human wounds have been aimed at protection, removal of exudate, inhibition of exogenous microorganism invasion, and improved appearance. Bacterial colonization or infection prevents healing of wounds and burns, resulting in delayed healing and potential conversion of the wound to a chronic state. Silver is important in the treatment of wounds due to its anti-microbial properties, and is therefore commonly used in the treatment of major burn injuries where bacterial infection is common. Development of advanced wound dressings that possess anti-microbial properties of wound surface and absorbed exudate to facilitate wound healing process is challenging study. Activated carbons are the most widely used industrial adsorbent for removing contaminants from gaseous, aqueous, and non-aqueous streams. Most of foam dressings are made from polyurethane (PU). Because PU foams contain a number of small pores that have the ability to pull exudate away from the wound bed. In this study, we fabricated anti-microbial PU foams containing silver nanoparticles and activated carbon. Then, the mechanical property, moisture absorption speed, absorptivity, morphology and cell viability of the composite foam were characterized. PU foams containing silver nanoparticles and activated carbon showed effective wound healing property compared to controls. Now, wound closure experiment for infected wound by bacteria is in progress.

Resume : Biomimetic materials are promising to bone tissue engineering due to their similarities with natural components of extracellular matrix. The potential applications of polymeric nanofibers have attracted the attention of several investigations because they usually show low toxicity, are biocompatible and biodegradable. However, polymeric nanofibers present unappropriated mechanical properties for bone tissue regeneration. For this reason, incorporated ceramic nanoparticles are largely used as scaffold in biological hard tissue growth. Carbon nanotubes (CNT) are used also as scaffolds in cellular growth in vitro improving the tenacity of the implanted material. The combination of these materials to the development of new biomaterial is very attractive for many applications. Therefore, the current project aims the production of new hybrid material by i) multi layered hydrophilic carbon nanotubes (CNT-O2) produced by plasma assisted vapor deposition, ii) hydroxyapatite nanocrystals (nHA) produced by electrodeposition and simulated body fluid immersion, and iii) Poly-acid lactic (PLA) nanofibers. The physical and biological properties of the new biomaterial were characterized. We succeed to obtain nHA/CNT-O2/PLA hybrid nanocomposites potentially applied to bone tissue regeneration.

Resume : Graphene has attracted strong scientific and technological interest in recent years. It has shown great promise in many applications, such as electronics, energy storage and conversion (supercapacitors, batteries, fuel cells, solar cells), and bioscience/biotechnologies because of its unique physicochemical and electronic properties such as high surface area (theoretically 2630 m2/g for single-layer graphene), excellent thermal and electric conductivity, and strong mechanical strength. Graphene also has numerous potential applications in biotechnology, including biosensing, disease diagnostics, antibacterial and antiviral materials, cancer targeting and photo thermal therapy, drug delivery, electrical stimulation of cells, and tissue engineering. Interactions of amino acids, DNA/RNA bases, and small molecules with graphene and carbon nanotubes are well studied using experimental and theoretical techniques. These studies indicate that noncovalent interactions such as π−π stacking and X−π (X = CH, OH, NH, etc.) stabilize the nucleobase and amino acid complexes of grapheme. Despite the importance of biomolecules–graphene interactions, a detailed understanding of the adsorption mechanism and features of biomolecules onto the surfaces of graphene is lacking. It is required the immobilization of biomolecules on the surface of graphene for design and production of bioelectronics devices. The interactions of biomolecules and graphene are long-ranged and very weak. Development of new techniques is very desirable for design of bioelectronics sensors and devices. Better understanding of interaction between amino acids with these 2D surfaces will provide better understanding of same interaction mechanisms for peptides and proteins. Because of its crucial biological roles such as cell and tissue remodeling, it makes possible to gain new know how. At the same time, the track and detection of amino acids will provide detection of several diseases by using biosensors. As an example, it is possible to diagnosis of malaria disease by detecting Histedine and diagnosis of several cancer types and Parkinson’s disease by detecting Leucine. In this work, we have performed density functional theory (DFT) with vdW-DF method calculations for exploring the adsorption geometries, adsorption energies, electronic band structures and adsorption dynamics of Histidine and Leucine (model amino acid)/graphene composite system. We also investigate the stability of the system via molecular dynamics simulations both vacuum and aqueous environment. It is also shown that how modify structural and electronic properties of amino acids on graphene by applied charging and perpendicular electric field.

Resume : Chlorofullerene C60Cl6 is known as a versatile precursor for synthesis of various water-soluble fullerene derivatives [1-4]. It is known, in particular, that Friedel-Crafts arylation of C60Cl6 leads to the formation of C60R5Cl derivatives bearing the appended fragments of arylalkylcarboxylic acids showing advanced biological properties [5]. However, these compounds are synthesized under harsh conditions using toxic nitrobenzene as a solvent and the product yields are disappointedly low. To solve the aforementioned issues, we have applied esters of thiophenylalkylcarboxylic acids for functionalization of C60Cl6, which resulted in the formation of C60R5Cl, C60R5H, C60R6 and other derivatives depending on the precursor structure and the reaction conditions. The selectivity of these reactions were approaching 80% in some cases. Using highly reactive thiophene-based reagents allowed us to perform the syntheses under mild conditions and apply 1,2-dichlorobenzene instead of toxic nitrobenzene as a solvent. Cleavage of the ester groups allowed us to prepare a series of novel water-soluble fullerene derivatives. Antiviral activity and toxicity of the prepared compounds will be discussed. 1. A. A. Yurkova et al, Chem. Commun., 2012, 71, 8916 2. A. B. Kornev et al, Chem. Commun., 2012, 48, 5461 3. E. A. Khakina et al, Chem. Commun., 2012, 48, 7158 4. E. A. Khakina et al, Org. Biomol. Chem., 2016, DOI: 10.1039/C6OB02251K 5. O. A. Troshina et al., Org. Biomol. Chem., 2007, 5, 2783

Resume : In order to probe the possible applications of graphitic Carbon Nano Onions (CNOs) as a platform for the diagnosis and treatment of Central Nervous System (CNS) pathologies, fluorescently labelled CNOs were stereotaxically injected in vivo in mice hippocampus. Their diffusion within brain tissues and their cellular localization were analyzed ex vivo by confocal microscopy, electron microscopy and correlative light-electron microscopy techniques. Results indicate that the diffusion of CNOs occurred from the injection site to the surrounding CNS tissues. Efficient internalization of the nanomaterial is evidenced from the fluorescence staining of neuronal cells populations. The CNOs injection produced no detectable toxicity over neuronal signal conduction. Moreover, no adverse effects on mice behavior were evidenced as well as confirmed from electrophysiology and behavioral studies performed on treated mice. These results give robust confirmation of the Carbon Nano Onions ability to interface with several cell types, and pave the way to their development as possible brain diseases-targeted diagnostics and/or therapeutics nano carriers. Acknowledgments: COST Action CA 15107 “Multi-Functional Nano-Carbon Composite Materials Network (MultiComp)”

Resume : Graphene oxide (GO) has shown great potential for many applications where electrical conductivity is not required and, on the contrary of single layer graphene, its preparation can be scaled up to high quantities. The oxygen-containing groups on its surface render it dispersible in water, and thus easier to manipulate, while allowing further chemical functionalization on the material. The assembly of 2D materials into 3D architectures can be a useful solution to make accessible the high surface area of these materials for storage of different types of molecules such as gases, drugs, etc. The objective of this work was to build a mesostructured 3D material made of graphene oxide layers separated by rigid tridimensional pillars. For this purpose, we used 4-(aminophenyl)methane (TKAm) as pillaring units and we proved our concept over both a commercial Hummers’ GO and a lab-made Hummers’ GO. Also, we tested two different reaction conditions for the functionalization of GO. One consisted in dispersing the GO monolayers into water so that the amine groups of TKAm linkers can have access to the α-carbon of the epoxy groups situated on the basal planes of GO [1]. The other approach consisted in exploiting the swelling properties of GO in polar organic solvents [2]. Thus, a solvothermal synthesis in methanol as solvent was tested. In both cases, the XRD analysis showed the formation of a pillared GO-based material with an interlayer distance of ~14 Å, which is 6-7 Å higher than that of pristine graphite oxide. By operating under solvothermal synthesis conditions, we were able to obtain a material with specific surface area (SSA) up to 13 times higher (660 m2/g) than that of the pristine GO. [1] W. Gao, Chem. Soc. Rev., 2010, 39, 61–95. [2] M. V. Korobov, A. V. Talyzin, A. T. Rebrikova, E. A. Shilayeva, N. V. Avramenko, A. N. Gagarin and N. B. Ferapontov, Carbon N. Y., 2016, 102, 297–303.

Resume : Molluscan nacre is a fascinating biomineral consisting of a highly organized calcium carbonate composite that provides unique fracture toughness and an iridescent color. Organisms elaborately control the biomineralization using organic macromolecules. A matrix protein Pif80 was discovered in the nacreous layer of the pearl oyster Pinctada fucata, and that has been regarded as an essential component to induce and regulate nacre formation. In this study, the gene encoding Pif80 was genetically redesigned for the recombinant production in Escherichia coli system, and the recombinant Pif80 (rPif80) was successfully expressed and purified. Through interactions with calcium ions, rPif80 induced the formation of amorphous calcium carbonate granules and stabilized these granules by forming calcium ion-induced coacervates. Under nacre calcification condition, the amorphous mineral precursors were destabilized by the re-dissolution of rPif80 coacervates, resulting in the growth of nacre-like nanogranular aragonite on the polysaccharide substrate. Our findings can give potential to understand biomineralization mechanism of nacre and to fabricate nacre-mimicking notable materials.

Resume : Over the past century, fossil fuel-based nonrenewable based polymers which are used extensively have created a lot of environmental problems. Because of these environmental concerns, there is naturally a great desire to find new resources and materials to replace petroleum-based materials. So in the last several decades there have been expanding research efforts focusing on new bio-based materials with high performance [1-3]. Biodegradable polymers are alternative materials for this solution, which have been developed and implemented in many areas. Poly(hydroxybutyrate-co-valerate), PHBV, is a biodegradable polymer which is formed in bacterial cells as an energy reservoir. However, some inherent properties of PHBV restrict the use of this polymer for a wide range of applications. Therefore, the modification of biodegradable PHBV polymer through innovative processing technology is an important task. Ongoing efforts to improve properties and performance of bioplastics are driven by wider market acceptance. In this study, PHBV based nanobiocomposites (PHBV/BN) were prepared with the incorporation of the various percentage of nano boron nitride (BN). The structure of PHBV/BN nanobiocomposites was investigated by FTIR, XRD and SEM. XRD and DSC studies showed an increase in crystallinity due to the addition of BN. TGA analysis showed improvement in thermal degradation behavior of the composites with an increase in boron nitride concentration. The oxygen and water barrier properties of PHBV/BN nanobiocomposites were measured. A substantial reduction in oxygen and water permeability due to increase in boron nitride loading was observed. Moreover, BN has been shown to contribute to the enhancement of mechanical properties. Acknowledgements M. Öner thanks the Scientific and Technological Research Council of Turkey (TUBITAK, Project No. 215M355), and M.Bechelany thanks the Campus France (PHC Bosphore No.35211XD) for funding this work under a Bilateral Cooperation Program between Turkey and France. References 1.J. M. Raquez, Y. Habibi, M. Murariu and P. Dubois, Prog.Polym. Sci., 2013, 38, 1504–1542. 2. M. Öner, A. A. Çöl, C. Pochat-Bohatier and M. Bechelany, RSC Adv., 2016, 6, 90973–90981. 2. N. Tenn, N. Follain, J. Soulestin, R. Cretois, S. Bourbigot and S. Marais, J. Phys. Chem. C, 2013, 117(23), 12117–12135. 3. V. Siracusa, P. Rocculi, S. Romani and M. D. Rosa, Trends Food Sci. Technol., 2008, 19, 634–643. 4. G. Braunegg, L. Gilles and F. G. Klaus, J. Biotechnol., 1998, 65(2), 127–161.

Resume : The aim of this study is the encapsulation of the polyphenolic compounds loaded on the crosslinked chitosan using various methods: self-crosslinking in high density ultrasonic field, ionic gelation. Such drug delivery systems show enhanced stability, solubility and protection from physical and chemical degradation with improved bioavailability to the gut and hepatic level. The contribution focused on the antioxidant properties of the polyphenols loaded on the chitosan nanoparticles and it is shown that the capacity of the free radicals scavenging rate is dependent of shape and the spongy structure induced by cross-linking in chitosan nanoparticles. In addition, the spongy structure is in direct relation with the loading capacity of the polyphenols.The antioxidant effect of the chitosan nanoparticles, polyphenolic compounds and of the biocomposites have been investigated in vitro non cellular by chemiluminescence and DPPH (2,2-diphenyl-1-picrylhydrazyl) methods. In addition, atomic force microscopy AFM and UV-Vis reveal a series of properties such as spectral characteristics and specific topography. DLS was used to measure the hydrodynamic size and polydispersity index Keywords: drug delivery nano systems, chitosan nanobiopolymers, polyphenolic compounds, antioxidant effect

Resume : Silver nanoparticles has been recognized as an antimicrobial component in therapeutic treatment for many years. There is increasing evidence that silver nanoparticles can promote wound healing and may also possess anti-inflammatory properties. Also, medicinal plants are a natural source of various pharmaceutical products with different biological activities offering treatment for several diseases. Herbal extract is a complex mixture of compounds, which can have antibiotic, antiviral, anticancer, antifungal, anti-inflamatory properties. Furthermore, association betwen silver nanoparticles and herbal extracts, can lead to a new biohybrids with enhanced therapeutic efficiency. The aims of the current paper were (i) to realize a new design for nano biohybrids based on silver nanoparticles and herbal extracts (ii) to evaluate the silver nanoparticles alone (iii) to evaluate the silver nanoparticles with surface modified by functionalization with various herbal extracts (aqueous, hydro alcoholic extracts and plants oils). In order to achieve this study were investigated hydrodynamic size, polydispersity index and zeta potential by dynamic light scattering technique and a series of properties such as spectral characteristics and specific topography by UV-Vis and AFM atomic force microscopy. In addition the viability of cells were detected by MTS - assay that emphasize significant stimulation of the growth of mouse fibroblast 3T3 in a dose-dependent manner. Keywords: Nano biohybrids, silver nanoparticles, herbal extracts

Resume : The structure-function relationship of conjugated polymers (CPs) interacting with various biologically active materials is of prime interest as the physical and biophysical properties of the complexes required for many applications are closely related to the nature of self-assembly. In this presentation, we report substantial structural differences of a set of four CPs containing the same positively charged side chains, which only different in the backbone chemical structure and connectivity, upon complexation with linear polyanion, glycosaminoglycan (GAG). Electronic spectroscopic data reveal that CP/GAG complexes form unique helixes depending on the nature of backbone and the type of GAG. The structure-property relationships can be useful for fabrication of highly ordered macromolecular materials for broad electronic or biological applications.

Resume : In the field of the synthesis and functionalization of inorganic nanoparticles (NPs) for biomedical applications, most researches aim at developing multifunctional theranostic NPs which can both identify disease states and deliver therapy and allow thus following the effect of therapy by imaging. The current challenge for iron oxide based NPs is the design of NPs able to combine in one nano-objects both magnetic hyperthermia (MH) and MRI with the best efficiency in order to reduce the dose injected in the patient. Ultra small iron oxide NPs are already commercially used as T2 contrast agent for MRI. The use of MH as a stand-alone or an adjacent therapy for cancer is closer to be a reality in every hospital thanks to the positive results achieved by the clinical trials carried out by MagforceTM(Germany) treating glioblastoma. Nonetheless, the need for direct intratumoral injection of large amounts of NPs to achieve a therapeutic effect only points out at the need of improving the available nanomaterials for MH. Different parameters may be varied to increase the effective heat loss of a ferrofluid such as size, shape anisotropy or composition, among others. Shape and aspect ratio may offer interesting possibilities as chain formation has been previously reported to increase heat loss. Furthermore there is also a need for evaluating the heating efficiency in cellular media as it may be different from that in solution. On that basis, plate-like, cubic and octopod shape NPs were prepared by thermal decomposition of home-made iron stearate, functionalised with dendron ligands to achieve aqueous suspensions and proved suitable for in vivo injection. MH performance was found to be shape-dependent with octopod-shaped NPs exhibiting the highest SAR values of 260 W.g-1 (f = 579 kHz, 8 kAm-1, ILP = 7.1 nHm2kg-1) or 960 W.g-1 (f = 796 kHz, 16 kAm-1, ILP = 4.8 nHm2kg-1). At the same time, their performance in MRI was investigated leading to relaxivity values of 16.9 and 405.5 mM-1 s-1 for r1 and r2, respectively, which was superior to that of commercial products like Resovist®. Finally, cell response was studied as a function of NP concentration and morphology, as well as under MH treatment. Therapeutic properties were also obtained by filling carbon nanotubes (CNTs) with ferrite NPs as heat mediator for photothermal ablation and as contrast agent for MRI respectively. They were capable of absorbing and efficiently converting NIR light into heat to generate thermoablative temperatures and cell lysis. They can be used as T2 agents for MR image-guided photothermal therapy. The obtained results open the possibility of using these systems as theranostic platform thanks to the exhibited performance in hyperthermia and MRI at the cell level.

Resume : Calcium phosphate (CaP)-based ceramics have a chemical composition very close to the mineral part of the bone. Biphasic, triphasic and multiphasic calcium orthophosphates have been considered as biomaterials for reconstruction of bone defects, dental and orthopedic applications. In general, this concept is determined by advantageous balances of more stable, frequently hydroxyapatite and more resorbable, typically tricalcium phosphates (Ca3(PO4)2, TCP), including α- and β-TCP phases of calcium orthophosphate composites, while the optimum ratios depend on the particular application. In most cases, the β-TCP is implanted into a bone structure in the form of granules or blocks (dense or macroporous scaffolds). In the past decades, β-TCP powders are reportedly prepared via conventional solid-state reactions, combustion or flame spray synthesis, chemical precipitation technique and sol–gel method. Namely, the precipitation technique, besides its low cost, has been widely used due to the better control of composition and physical properties of obtained powders. In the present work, for the synthesis of tricalcium phosphate powders a novel wet polymeric precipitation method in an aqueous PVA solution has been developed. The formation of β-TCP ceramics synthesized by polymeric precipitation method requires 800 °C temperature, as determined by TG-DSC analysis. The XRD analysis results, before and after calcination, confirmed that single phase β-TCP powders were obtained at rather low temperature (800 °C). Moreover, the formation of β-TCP occurred via transformation of the nanocrystalline Ca-deficient hydroxyapatite (CDHA) phase into β-TCP. The SEM micrographs of β-TCP samples synthesized by polymeric precipitation method showed that spherically shaped particles 100–300 nm in size have formed after heat treatment at 800 °C. Besides, the synthesized β-TCP powders showed a narrow and homogeneous particle size distribution. From these β-TCP powders the bars of 6.46 x 4.35 mm size were pressed for further animal in vivo histological investigations. Fabricated β-TCP specimens were placed to the holes drilled in the bones of the rats and maintained for 4 weeks. These specimens are currently under investigation. This work was supported by a grant KALFOS (No. LJB-2/2015) from the Research Council of Lithuania.

Resume : Infections induced by bacterial biofilm formation on medical devices such as implants or catheters are recognized as a significant problem. Development of specific materials which inhibit microorganisms’ attachment and/or retard biofilm formation by reducing bacterial proliferation is required to solve this problem. In this study, we propose an antibacterial coating material based on biocompatible titanium, that is, titanate nanosheets (TNS). TNS was synthesized by a simple hydrolysis reaction using titanium (IV) tetraisopropoxide and tetramethylammonium hydroxide. The particle size of the resulting TNS, measured by the dynamic light scattering method, was under 10 nm. It dispersed in a solution stably, and the colloidal solution of TNS was transparent. The antibacterial effect of the colloidal solution was evaluated by a colony forming units counting method. The result showed that higher concentrations of TNS solution exhibited greater antibacterial effect. Though the TNS absorbs tetramethylammonium cations (TMA+) because of the negative charge, this TMA+ did not exhibit any antibacterial effect at all. This result implies that the TNS material itself has an antibacterial effect and the mechanism is assumed to physically damage the bacteria. Moreover, TNS exhibited an inhibition effect on bacterial agglutination. This will be also useful to help prevent biofilm formation on medical devices.

Resume : PHBV (3-polyhydroxybutyrate-co-3-hydroxyvalerate) is a bio-based and biodegradable polymer derived from bacterial fermentation. It possesses comparable properties to conventional plastics; however, its relatively low thermal stability and brittleness limits its industrial usage. Incorporation of nano-sized inorganic particles into PHBV matrix is a novel method for overcoming the limitations of thermal and mechanical properties [1-3]. ZnO (zinc oxide) particles are a popular additive for polymer matrices due to bio-compatibility, high elastic modulus, and high thermal and chemical stability. Nevertheless, particles are known to form agglomerates during wet synthesis and during incorporation into organic polymer matrices. Agglomeration is an important phenomenon that should be prevented, since it hinders improvement of polymer nanocomposites properties. Surface modification is one method to increase the compatibility between the organic polymer and inorganic particle interface and thus reduce particle agglomeration. Ultrasonic cavitation is another method effective in dispersion of inorganic nanoparticles within suspensions. In this study, rod-shaped ZnO particles were synthesized by chemical precipitation method [4]. Ultrasonic dispersion was applied to the particles in combination with surface modification prior to incorporation into PHBV matrix by melt-extrusion. Mechanical properties of the biocomposites were analyzed and compared to those of neat PHBV. [1] Srithep, Y.; Ellingham, T.; Peng, J.; Sabo, R.; et al. Polym. Degrad. Stab. 2013, 98 (8), 1439. [2] Silverman, T.; Naffakh, M.; Marco, C.; Ellis, G. Mater. Chem. Phys. 2016, 170, 145. [3] Bekat, T.; Öner, M. Pure Appl. Chem. 2016, 88 (10–11), 1027. [4] Akin, B.; Oner, M. Res. Chem. Intermed. 2012, 38 (7), 1511.

Resume : Peptide aptamers with affinity for inorganic target materials have been selected from phage-display screening and have been widely used in construction of bio-inorganic interfaces. However a critical point in the bio-panning was an elution step of objective phages from phage-target complexes, because it was difficult to recover the intact phage bodies with high affinity peptide-aptamers from the complexes. For the purpose of harvest of peptide aptamers with high affinity for inorganic-material nanoparticles (NPs), we transferred phage-DNA into bacterial cells using an electroporation with intact phage-NPs complexes directly bypassing the elution process. We have successfully obtained a novel peptide aptamer (named ST-1 with the sequence AYPQKFNNNFMS) with highly strong binding activity for TiO2 by the easy and rapid screening method. A cage-shaped protein fused with both ST-1 and an available carbon nanotube-affinity peptide could efficiently mineralize a titanium-compound around the surface of carbon nanotubes (CNTs). The titanium-compound-CNT complex incorporated in the photo-electrode of a Dye-sensitized solar cell boosted the solar cell performance. This peptide aptamer selection method makes it possible to isolate phages bound with target materials most strongly, and also the procedure is simple and rapid for selection of aptamers in the process of phage-display screening.

Resume : Self-assembly is a process in which a disordered pre-existing constituent autonomously forms an organized structure or pattern without any human intervention. This natural process, received growing interest as a bottom-up nano fabrication tool for designing biocompatible, biodegradable, inert and bio-functional peptide based bioinspired nanomaterials. Recent advances showed us that the self-assembled peptide nanostructures provide an appropriate platform for regenerative medicine, tissue regeneration and stem cell differentiation due to self-supporting and extracellular matrix mimicking properties. Thanks to the dynamic nature of self-assembled peptide nanostructures, morphological and supramolecular chirality of self-assembled peptide nanostructures affect the biological responses. Here, we study various self-assembly conditions and self-assembly mechanism of peptide amphiphiles synthesized with different molecular and supramolecular chirality. Switch in the trigger forces such as pH change or charged molecules in the system, and amino acid sequence modifications in the secondary structure-forming region of peptide amphiphiles lead to self-assembled nanostructures with different morphologies. We showed that, type of amino acid residues and trigger forces effects to bonding ability and morphologies as a result. These supramolecular chiral peptide nanostructures were studied in detail by several spectroscopic techniques and in situ and ex situ imaging methods.

Resume : The Silver nanoparticles (Ag NPs) were synthesized in a green way using by Zingiber officinale extract as a reduction agent. Zingiber officinale extract were poured into 0.2mM AgNO3 and after half an hour AgNPs formation were started. The change of color from colorless to light yellow, brown and reddish brown, respectively, is the first indication of Ag NPs formation. Next step, ultraviolet-visible (UV) spectroscopy was used to confirm the formation of Ag NPs. Moreover, transmission electron microscopy (TEM) showed the Ag NPs size between 5 to 25 nm. Antifungal activity of synthesized Ag NPs was studied by minimum inhibitory concentration (MIC) method against Candida albicans fungi and compared with Fluconazole antifungal drug. The MIC outcome revealed that Ag NPs synthesized by Zingiber officinale are more powerful than Fluconazole drug against Candida albicans. In conclusion, the aforementioned Ag NPs could be an appropriate alternative candidate for Fluconazole.

Resume : In this lecture, I will discuss some recent developments in the advanced optical imaging systems and biomedical devices in our group. I will first present the development of various nanoparticles for sensing the pH value in cellular environment. By surface functionalization schemes, it is possible to control the location of nanoparticles in cells allowing us to track the local pH value around the nanoparticles inside cancer cells. The acidification process of nanoparticles in the endocytosis process can be recorded. Such technique can be extended to detect the local chemical reaction inside living cells. As for in vivo imaging, we have utilized the multi-photon microscopy to investigate the disease models with the help of nanoparticles. I will discuss the applications of multi-photon imaging in various mouse models. On our multi-photon platform, it is possible to track the movement of various types of cells including platelets, white blood cells, red blood cells, tumor stem cells and nanomaterials in mouse models using surface modified nanoparticles at a frame rate as high as 100 frame/s. I will also summarize our recent development of the circulating tumor cells (CTCs) isolation chips. CTCs are cancer cells that break away from a primary tumor or metastatic site, escape from immunosurveillance, and then circulate in the peripheral blood with the capability of forming distant metastases. "Liquid biopsy for CTC detection" provides no radiotherapy side effect and can be carried out routinely in patients at all disease sites. Although the tumor liquid biopsy can be easily used for collecting CTCs, the identification of CTCs in patient blood samples is technically challenging because of the extremely low concentration of CTCs among a large number of hematologic cells (red blood cells and leukocytes). To address this unmet need for rare cell isolation, we have developed substrates using the synergistic effect of nanomaterials and biological immobilization of CTC markers for enhancing CTC capture efficiency during a liquid biopsy procedure. In addition to the pursuit of high-cell-capture yield and specificity from human blood on chips, further vertical integration for the downstream characterization of CTCs is required for future CTC chips, such as liquid biopsy, for achieving a variety of clinical applications. In our approach, we have employed three-dimensional (3D) conducting polymer-based bioelectronic interfaces (BEIs) that can be integrated on electronic devices for rare circulating tumor cell (CTC) isolation, detection, and collection via an electrically triggered cell released from chips.

Resume : The inaugurations of the new generation synchrotron and X-ray Free Electron Laser facilities mark an important milestone on the development of X-ray science. The impact of these new facility to the nanoscience and nanotechnology is also become visible. The speaker will use two examples, to suggest the bright potential of X-rays imaging, which is an area taking full advantage of the offer of these new opportunity. One the application synchrotron X-rays, phase contrast imaging and transmission X-ray microscopy demonstrate the capability to impact life science by tackle important questions, such as the tumor related micro-angiogenesis. With the capability to characterize quantitative all the structural factor of the microvasculature of complete tumor region or an organ, aided with the innovative use of nanoparticles, we could conclude that the phenotype dependent tumor angiogenesis in mouse glioma models. We also used the SACLA (RIKEN/HARIMA, Japan) X-ray free electron laser (X-FEL) to implement coherent diffraction imaging (CDI) of individual liposome particles in water, with or without inserted doxorubicin nanorods. In spite of the low cross section, the diffracted intensity of blank (drug-free) liposomes was sufficient for spatial reconstruction yielding quantitative structural information. When the particles contained doxorubicin, we could measure the structural parameters of the nanorods. In both cases, the information went well beyond what can be obtained by small-angle X-ray scattering (SAXS) and electron microscopy. This is important for the potential drug efficiency optimization and, in general, for X-FEL analysis of individual low-cross-section nanoparticles.

Resume : Nanomaterials have been widely applied to advance clinical diagnostics and therapeutics. A novel approach for synchronizing hyperthermia and thermal-responsive local drug release was realized through targeting probe combined a magnetite nanocrystal (Fe3O4@PSMA) core and a polynucleotide shell carrying 5-fluorouracil (5-FU) and anti-human epidermal growth factor receptor 2 (anti-HER2) antibody for cancer-cell-specific targeting. The probes play not only as a MRI molecular imaging contract agent for confirming disease location, but also serve as an important relay for externally delivered radiofrequency energy for tumor hyperthermia and drug release. Pathological examines and in vitro study show that this synchronization is significantly more efficacious in both in vitro and in vivo models than hyperthermia or chemotherapy alone. Prominent tumor remission in vivo was achieved through radiofrequency synchronization of hyperthermia and chemotherapy after the nanoparticle had been intravenously injected. For the infectious disease management, we showed its efficacy in the treatment of Clostridium difficile infection (CDI). CDI has emerged to be a major cause of healthcare-associated infection in the world. Resistance of CD spores to various preventive and therapeutic measures post a significant threat in CDI. Nanomaterials have been explored for potential applications in anti-microbials with intrinsic advantages of low drug-resistance issue and high efficacy. We discovered a specific truncated octahedral Fe3O4 single crystal nanoparticles with a strong inhibitory effect to CD spore germination in vitro and in vivo. The 22 nm presented excellent saturation magnetization (94 emu/g) close to the bulk due to the presence of alpha iron in the crystal. Such particle showed a dose dependent inhibition of CD spores germination (62% growth inhibition at 50 µg/mL) for 20 minutes of exposure. At 500 µg/mL, the inhibition reached a degree close to that of sodium hypochloride. CDI animal model established in NF-?B-reporter mice using oral gavage with CD presented significant inflammation in control mice compared to the nanoparticle treated group as revealed by in vivo Imaging System. Cryo-electron tomography clearly showed binding of the nanoparticles to CD surface followed by disruption of CD spores. Pro-inflammatory cytokines including IL-1?, TNF-?, and INF-? were significantly suppressed upon nanoparticle treatment. These results provide nano-structural based strategy of CDI control and potential mechanisms thus encourage further clinical translational development.

Resume : Cell membranes present a unique interface that governs numerous biological events in physiology as well as in disease pathogenesis; exploiting this interface for nanoparticle functionalization promises enhanced biocompatibility and novel treatment modalities with biomimetic functionalities. Precise control over nanoparticle surface charge modulates the nanoparticle?s surface energy and influences its interaction dynamics with biological components. Using polymeric nanoparticles consisting of carboxylated poly(lactic-co-glycolic acids), a biodegradable polymer commonly used for drug delivery, we demonstrate surface density of the carboxyl groups strongly influences nanoparticle interaction with cellular membranes. In particular, we observed that below a surface density of 0.65 carboxyl groups per nm2, cellular membranes cloak over the polymeric nanoparticles under dispersion. The cloaking process is efficient and self-limiting, resulting in complete, unilamellar membrane coverage. Close inspection of the cell membrane cloaked nanoparticles shows that the membranes are oriented right-side-out, which can be attributed to the asymmetric nature of cellular membranes. Cell membranes formulated with positively charged particles also yields interesting insight as they result in particle-adsorbed membrane vesicles rather than membrane cloaked particles. These observations suggest a subtle attractive interaction behind the cell membrane cloaked nanoparticles. Analysis has been performed to validate that the cell membrane cloak effectively functionalizes nanoparticles with membrane membrane proteins and surface glycans, bestowing the nanoparticles a biomimetic surface for biological interactions. The technique has been applied to cellular membranes derived from red blood cells, platelets, and cancer cells, and the resulting nanoparticles have been shown to adopt numerous cell-like functionalities, including cell-like interactions with the immune system, toxins, pathogens, and endothelium. Several therapeutic applications, such as long-circulating drug delivery, targeted drug delivery, biodetoxification, vaccine preparation, and pathogen isolation were demonstrated. The biomimetic nanoparticles have therapeutic potentials in treating cancer, cardiovascular disease, autoimmune disease, and infection. They may also be engineered as an advanced diagnostic tool.

Resume : Here we have demonstrated the operation of conducting polymer-based bioelectronic interfaces (BEIs) as two functional swimming pools on organic electrochemical transistors (OECTs), which can be used for rare circulating tumor cell (CTC) isolation and detection. It is noteworthy that one kind of novel three-dimensional OECT (3D-OECT) devices was developed for the CTC enrichment via an electrically triggered cell released from one chip, and another planar type OECTs was used for identifying cell density of four different cancer cell lines. To develop the 3D-OECT based swimming pool system, we used the chemical oxidative polymerization of carboxylic acid?modified 3,4-ethylenedioxythiophene and modified poly(dimethylsiloxane) (PDMS) transfer printing technology. The high-aspect-ratio structures of poly(3,4-ethylenedioxythiophene) (PEDOT)-based "nanorod" arrays can be obtained on the OECT active channel layer when using the Si "microrod" arrays as masters. Then, we integrated the biotinylated poly-(L)-lysine-graft-poly-ethylene-glycol (PLL-g-PEG-biotin) coating with 3D PEDOT-based BEIs for dynamic control of the capture/release performance of CTCs on chips; this combination exhibited high cell-capture efficiency from EpCAM-positive MCF7 cells while maintaining high resistance from the EpCAM-negative Hela cells adhesion after 1 h of incubation. Due to the outstanding electrochemical doping/dedoping and low-impedance properties of PEDOT materials, the captured CTCs can be triggered to electrically release through the desorption phenomena of PLL-g-PEG-biotin. More than 90% of the captured cells can be released while maintaining very high cell viability. We also demonstrated that, the planar-type OECT based swimming pool system for the cell-sensing, we prepared the high electrical conductivity of PEDOT-based active channel layers on planar type OECTs for monitoring CTC-capture performance on chips and identifying the cancer cell phenotypes. Evidence suggesting that this study opens an avenue of bioelectronic medicine for rapid cancer diagnostics.

Resume : Organic materials incorporating functional polypeptides that exhibit biological activities similar to growth factors and extracellular matrices can be regarded as bioinspired, bioactive materials, because such materials can induce biological signals in living cells through specific interactions with cell surface receptors. Such a bioinspired strategy provides a variety of biomaterials capable of biological regulation of cell behaviours, such as cell survival, proliferation, differentiation and function. This paper presents our attempts to demonstrate the feasibility of genetic engineering to design and construct such polypeptide-incorporating materials. In the first attempt, a cell adhesive polypeptide, derived from extracellular matrix laminin, was genetically engineered to link a collagen-binding peptide. The chimeric polypeptide was expressed in E. coli and simply but firmly incorporated into collagen hydrogels. The composite hydrogel was evaluated in vitro and in vivo for its feasibility to provide an appropriate microenvironment for neural progenitor cells. The results showed that the hydrogel systems served to improve the survival of the cells transplanted into the brain by blocking the infiltration of inflammatory microglia and providing an adhesive substrate to the transplanted cells. A similar strategy could be applied for incorporating epidermal growth factor (EGF) into collagen hydrogel by fusing a collagen-binding polypeptide at the terminus of an EGF domain. In the collagen hydrogel networks incorporating EGF, we observed that proliferation and survival of neural progenitor cells were significantly enhanced. The examples described above demonstrate that matrix-binding functional polypeptides can be synthesized by fusing an adaptor peptide at the terminus. This strategy is quite robust and opens a variety of applications especially in the design of biologically active materials that provides optimized microenvironments for living cells.

Resume : Naphthalene diimide, ND, derivatives form a stable complex with a DNA duplex, where two of their substituents are located in either grooves of DNA duplex and act as an anchor to prevent the complex from dissociation. Since ND barely stabilizes single stranded DNA, this phenomenon is specific to double stranded DNA. We synthesized FND, ND carrying two ferrocene moieties to enable electrochemical gene detection. Target genes were detected specifically through the electrochemical signal of FND concentrated on the hybrid with a single stranded DNA probe-immobilized electrode.1 Recently, we found that FND derivatives serve as a strong tetraplex DNA binder and applied them to electrochemical detection of telomerase activity. This is based on the detection of a tetraplex DNA generated by telomerase. Since telomerase activity is high only in cancer cells, this method may be applicable to cancer diagnosis. We developed further oral cancer diagnosis for exfoliated oral cells in collaboration with dentists.2-4 The cyclic ND linkage connecting the substituent termini is expected to improve selectivity for tetraplex DNA binding because of its diminished affinity for DNA duplexes. In fact, cyclic ND showed higher affinity for ta-core DNA carrying part of a telomere DNA sequence5 Cyclic ND carrying a ferrocene part in the linker chain also showed high affinity for TA-core DNA. These observations should help realize electrochemical cancer diagnosis based on FND. To improve binding affinity for tteraplex DNA, cyclic perylene diimide, cPDI, was synthesized by connected with two linker chain from amide nitrogen atoms. cPDI strongly bound to TA-core carrying the part of human telomere DNA sequence and expecting to form hybrid type tetraplex structure. cPDI has a 103-times preference for tetraplex structure than for double stranded one. According to telomerase inhibition assay, cPDI has 0.3 ?M of IC50 value and furthermore cPDI bound to tetraplex DNA generated with telomerase and stabilized to inhibit the telomere reaction. These results showed the possibility of cPDI as an effective anticancer drug. This work was carried out as collaborative research between Kyushu Dental University and Kyushu Institute of Technology. I appreciate the significant contribution made by researchers who appears in the following papers. References 1. S. Takenaka et al., Anal. Chem., 72, 1334-1341, (2000). 2. K. Mori et al., Clin. Chem., 59, 289-295 (2013). 3. S. Takenaka and S. Sato, "Telomerase as a biomarker for oral cancer," Biomarkers in Cancer, Victor R. Preedy, Patel & B. Vinood, Eds., Springer pp. 753-770 (2015). 4. S. Sato and S. Takenaka J. Inorg. Biochem., 167, 21-26 (2017) 5. Y. Esaki et al., Chem Comm., 50, 5967-5969 (2014).

Resume : Titanium dioxide (TiO2) decomposes organic contaminants adsorbed on its surface via its photocatalytic activity, triggered by UV irradiation. This phenomenon has been applied commercially in self-cleaning glass windows and coatings. In pursuit of developing a novel technique for engineering biointerfaces, we recently began to explore an application of TiO2 photocatalysis to locally alter the affinity of scaffold surfaces to living cells. Here, we describe how this method can be employed to pattern neuronal cells and networks. A thin layer of TiO2 was sputtered onto a glass coverslip, and the TiO2 surface was modified with n-octadecyltrichlorosilane (OTS) to make it cell-repellent.?By irradiating the OTS region with UV light and inducing subsequent adsorption of scaffolding molecules, PC12 cells and primary rat hippocampal neurons could be patterned both ex situ and in situ. Passive adsorption of extracellular matrix proteins was sufficient for supporting the growth of PC12 cells but not primary neurons. To create an adhesive domain for primary neurons, the proteins had to be actively cross-linked to the selected region. This was achieved by coupling laminin to the RPL2 protein, which has strong affinity toward metal oxides, including TiO2. With further improvements, the TiO2-assisted photocatalytic lithography would provide a key technology for fabricating living neuronal circuits with defined network topology and studying structure-function relationships in neuronal networks.

Resume : A recent survey reported by Chan and co-workers suggests that the delivery efficiencies for cancer nanomedicines are low-only 0.7% of an injected dose of nanoparticles ends up in a tumor- and not improving in the past ten years. To accelerate the clinical translation of nanomedicine and make nanotherapeutics for cancer a reality, factors that could significantly affect the in vitro and in vivo behaviors of nanoparticles should be adequately considered and investigated. Enhanced permeability and retention (EPR) is a key feature of tumor blood vessels and has been extensively used in the nanomedicine, such as Doxil (PEGylated liposomal doxorubicin) for the treatment of Kaposi's sarcoma. In general, EPR-mediated passive targeting highly relies on the prolonged circulation time of nanocarriers. Particularly important two parameters, that is, (1) nanocarrier size and (2) surface property are expected to play a key role on the pharmacokinetics and the biodistribution of the carrier material. In general, the injected materials would be recognized and bound rapidly by serum opsonins, followed by phagocytosis by macrophages and substantially accumulated in both the liver and the spleen (also known as the reticuloendothelial system). Previously, comprehensive studies highlighted protein corona neutrality as an important design in the development of targeted nanomaterial delivery and demonstrated that even a small difference in the surface heterogeneity could result in profoundly different interactions with cells and tissues. Therefore, the control and understanding of protein corona composition are critical for successful EPR-targeted nanomedicine. Mesoporous silica nanoparticles (MSN) are intriguing nanocarriers for efficient and cell-specific delivery of proteins, enzymes, and anti-cancer drugs to improve treatment of diseases. However, despite often highly promising in vitro findings, such as enhanced uptake and intracellular processing as well as efficacy, few in vivo evaluation of MSN are dedicated to investigating how the protein corona formed on nanocarriers in complex biological media mediate the in vivo tumor accumulation of nanocarriers. Here we systematically examined the effect of size and the surface heterogeneity (i.e. spatial arrangement and relative exposure of surface amines) of MSN on their biological fate both in vitro and in vivo. Four types of MSN with zeta potentials of around +35 mV and various diameters (50 and 200 nm) were chosen. First, we prepared well-suspended MSN by PEGylation (MSN@PEG) and simultaneously decorated them with positively charged ligands polyethyleneimine (PEI) or quaternary ammonium salts (TMAC). Then, interactions between these nanoparticles and Raw 264.7 macrophages as well as HeLa cells were studied in serum-containing media. Also, the impacts of these nanoparticles on cell cycle, autophagy, oxidative stress and hemolytic activity were investigated. Most importantly, by using the in vivo two-photon fluorescence imaging system, dramatic effects of the surface heterogeneity on blood circulation time were observed following intravenous injection of MSNs. Extremely noteworthy is 50 nm of MSN@PEG/TMAC showed highly tumor-targeting efficiency under IVIS investigation. This study would help us to clarify the relationship between synthetic identity, biological identity, and physiological response, and most importantly, develop a clinically translatable silica nano-platform for delivering theranostics.

Resume : Nanostructed substrates has been designed to simulate complex extracellular environments and monitor dynamic biological process at single cell level. When nanotopographic structures are being used to elucidate how physical cues influence cell behavior, the problems of detecting or sensing how cell feedback on nanotopographic structures are required to fully understanding cell-substrate interaction. A robust nanopillar platform with greatly increased spatial resolution now reveals that the forces deflecting beta1-integrin-rich perinuclear nanopillars are significantly higher than at the cell periphery. These forces originate from stress fibers spanning the nucleus as confirmed using pharmaceutical inhibitors, expression of KASH dominant-negative mutants and LMNA knockout. As the nanopillar pitch size is smaller than typical adhesions, single perinuclear stress fibers bind and pull multiple nanopillars into transient clusters. During cell migration, actin cap associated perinuclear stress fibers translocate gradually without losing tensile strength, suggesting that actin filaments are breaking away at the rear of each ?-actinin crosslinked stress fiber, while new ones join, which requires opening and closing of ??-actinin zippers?. Perinuclear adhesions might thus play far more important roles in rigidity sensing and mechano-chemical signal conversion than previously thought.

Resume : In our previous study, we developed mesoporous silica nanoparticles (MSN) as an enzyme delivery approach to successfully deliver superoxide dismutase (SOD) and glutathione peroxidase (GPx) into cells. Results demonstrated that these denatured antioxidant enzymes conjugated on the MSN surface could be delivered and refolded with specific enzyme activity to protect cells attacked by ROS. The approach not only overcomes the challenges of protein delivery, including poor stability, membrane impermeability and endosome trapping/digestion, but provides the following advantages: (1) one-step protein conjugation and purification, (2) easy mass production and (3) multiple enzyme delivery to regulate cascade reactions. While this approach shows potential development of preclinical protein therapy, an ideal nanocarrier applied in vivo needs to be more biocompatible, have increased stability, and avoid accumulation in organs after administration. This study therefore aims to improve the delivery approach to achieve the above properties by adding polyethylene glycol (PEG) and polyethyleneimine (PEI). First, biocompatible PEGylated MSN conjugated SOD were prepared and characterized. Then, we focused on the mechanism study in detail by comparing the difference between native SOD and denatured SOD conjugated MSN after cell delivery. To mimic the real environment in vivo, in vitro cell related studies were also carried out in serum-containing media condition. Protein structure was revealed by circular dichroism. We found that denatured SOD has better enzyme activity than native SOD when conjugated to MSN. We propose denatured SOD has less steric hindrance on MSN, which promotes efficient delivery resulting in enhanced enzyme activity.

Resume : We will report our recent progress in the development of advanced imaging systems. We will discuss how to use various surface modified nanoparticles for bioimaging including quantum dots and mesoporous nanoparticles. By various surface functionalization schemes, it is possible to control the location of nanoparticles both in vitro and in vivo allowing the measurement of chemical environments inside cells and tumors. To observe the behavior of nanoparticles in animal model, we have employed two-photon microscopy to study the real-time distribution of nanomaterials in the blood vessels. Since the penetration of infrared radiation is still limited to less than 1 mm from the surfaces of skins, we developed blood vessel observation technique on the earlobes of mice. When the drug loaded nanoparticles were injected in tail vein, the real time distribution of these nanoparticles in the blood vessels on the earlobes can be observed directly. To further evaluate the targeting effect of drug to tumor tissue. We have developed tumor model on the earlobes of mice by inoculating RFP-BXPC3 pancreatic cancer cells. The surfaces of nanoparticles were modified by antibody. After 10 minutes of injection at tail vein, the accumulation of nanoparticles can be clearly seen at tumor site. The increase in the nanoparticles can be observed by time-lapse images. Circulating tumor cells (CTCs) are cancer cells that break away from a primary tumor or metastatic site, escape from immunosurveillance, and then circulate in the peripheral blood with the capability of forming distant metastases. Two photon microscopy was used to study the tumors and their microenvironment. When CTCs are in circulation, the imaging system allows us to track the movement of individual CTCs in the blood vessels around tumors.