Converging technology for nanobio applications

Resume : Engineered nanoparticles are essential components in the development of nanotechnologies. For applications particles need to be functionalized to ensure a good dispersibility. In many cases however, functionalization is not sufficient. Particles dispersed in biofluids for instance become either coated with proteins or precipitate. Here we study the interactions between oxide nanoparticles (Ce, Fe) and living cells (fibroblasts, lymphoblasts, macrophages). By changing the coating from ligands to polymers, we show that the colloidal stability of the dispersion is improved and the adsorption/internalization towards cells is profoundly affected. As a result, precipitating particles interact more strongly with cells and the toxicity threshold are easily met. PEGylated neutral coating shows exceptional low uptake, of the order of 100 femtogram of iron per cell, i.e. 100-1000 less than with poorly coated particles. The present approach demonstrates that the surface chemistry of engineered particles is a key parameter of the nanoparticle/cell interactions, and has a strong impact on toxicity and cell viability. These results also pose the question of the ubiquity of the ?protein corona? and of its relevance in the context of nanomedicine related applications. M. Safi et al. Biomaterials 32, 9353-9363 (2011) A. Galimard et al., Small 8, 2036-2044 (2012) N. Ould-Moussa et al., Nanotoxicology (2014)

Resume : Controlling and improving neural/glial cell migration and neurite outgrowth are critical elements for tissue engineering applications and for developing artificial neuronal interfaces. In the nervous system, during tissue development or reconstruction, neural cells probe (through filopodia and neurites) and read extracellular stimuli from the micro/nano-environment within which they exist, retrieving essential directionality and wiring information. By exploiting electron beam and soft lithography we engineered polydimethylsiloxane (PDMS) nano and micro-structured membranes for nerve repair applications. Our substrates were patterned with gratings having ridge and groove widths between 500 nm and 10 μm. These gratings were used as scaffolds to study neuronal contact guidance and primary Schwann cell shaping, migration and wound-healing in vitro. Our results identify specific topographic elements that may be exploited for the production of new microdevices for enhancing nerve regeneration by promoting Schwann cell invasion, proliferation, terminal differentiation and neuronal migration. In vivo application of our microstructured membranes in a rat model of median nerve trauma will be finally discussed.

Resume : Graphene oxide (GO) [1-2] is a composite material obtained by means of exfoliation in water, using sonication, of graphite oxide. GO exhibits an excellent water solubility, low toxicity, and ultrahigh specific surface area, and it is more and more studied as nanoplatform in theranostics [3]. In fact, the chemical functionalization can dramatically change the GO?s properties. In particular GO modified could be adaptable for various applications such as optoelectronics [4], drug-delivery vehicles [5] and biodevices [6]. In this study we present a comparison between GO and R2N-functionalized GO in terms of spectroscopic, optical and binding potentiality features for biological sensing and drug delivery. In more details, we functionalized in graded way the GOs nanostructures to tune the surface properties and build a biocompatible platform for fluorescence imaging and drug delivery. Dye-labeled phospholipids were immobilized by physisorption as image contrast agents, while curcumin, a polyphenolic substance with antioxidant, anti-inflammatory and antineoplastic pharmacological actions, was loaded into the GO-based platform. MD simulations of both GO and functionalized GO were carried out to estimate the binding energy of the aggregates. Moreover, the samples were characterized by atomic force microscopy under air and physiological conditions, zeta potential, light scattering, Raman, fluorescence and UV-vis spectroscopy. The cellular uptake of the GO theranostic agent was followed by laser confocal scanning microscopy. [1] Liao KH, Mittal A, Bose S, Leighton C, Mkhoyan KA, Macosko CW, ACS Nano, 2011, 5:1253-8. [2] Mei XG, Ouyang JY, Carbon, 2011, 49:5389-97. [3] Zhang M, Cao Y, Chong Y, Ma Y, Zhang H, Deng Z, Hu C, Zhang Z, CS Appl. Mater. Interfaces 2013, 5, 13325−13332 [4] Xu Y, Liu Z, Zhang X, Wang Y, Tian J, Huang Y, Ma Y, Zhang X, Chen Y, Adv. Mater., 2009, 21: 1?5. [5] Zhang X, Huang Y, Wang Y, Ma Y, Liu Z, Chen Y, Carbon, 2009, 47: 334?7. [6] Mohanty N, Berry V, Nano Lett., 2008, 8: 4469?76

Resume : The search for regenerative agents that promote neuronal differentiation and repair is of great importance. In our study, we developnew nanoparticle-based platformsto enhance and direct neuronal growth. We examine the effect of nanoparticles as free compounds or attached to 2D and 3D substrates. Different sizes and materials, including silver, gold and iron oxide nanoparticles are tested. We grow neuroblastoma cells on surfaces coated with silver nanoparticles and find that the silver nanoparticles function as favorable anchoring sites, leading to a significantly enhanced neurite outgrowth. A comparison with other materials demonstrates a clear silver material-driven promoting effect in addition to itsnanotopography. The use of silver nanoparticles that are known as antibacterial agents suggestssilver nanoparticles as an attractive nanomaterial – with dual activity – for neuronal repair studies.Next, we covalently conjugate NGF (Nerve Growth Factor) to iron oxide nanoparticlesand study the effect of the novel complex on the differentiation process. We find thatthe nanoparticle-based treatment significantly promotes neurite outgrowth and increases the complexity of the neuronal branching trees. NGF, which is an essential contributor to neuronaldifferentiation and for centralneurodegenerative diseases treatment, undergoesslower degradation when linked with the nanoparticles. The iron oxide nanoparticles also enable magnetic manipulations that affect neuronal location and pattern.We propose a wide range of roles for nanoparticles as tools for manipulation of neurons underlining therapeutics potential.

Resume : Biomedical applications of nanodiamond (ND) have been investigated extensively due to its low toxicity, non-bleaching fluorescence, and high extensibility of the surface functionality through covalent organic functionalization. For in vivo applications such as drug carrier and imaging probe, ND should form a stable hydrosol under a physiological environment. In this context, we recently found that polyglycerol (PG) functionalization is very effective to impart the sufficient solubility and stability to ND [1]. In addition, the stable hydrogel of PG-functionalized ND (ND-PG) enabled precise characterization of the chemical structure by solution phase NMRs. Quantitative analyses were also conducted by elemental and thermogravimetric analyses. The ND-PG was subjected to further organic transformations at a number of hydroxyl groups on the PG layer to add more functions. As a result, we successfully prepared the ND-based drug carrier with platinum drug [2] and plasmid DNA [3], and MR imaging probe with gadolinium [3] and applied them to in vivo and in vitro evaluations. [1] L. Zhao, N. Komatsu, Angew. Chem. Int. Ed., 50 (6), 1388-1392 (2011) [2] L. Zhao, N. Komatsu, X. Chen, submitted [3] L. Zhao, H. Kojima, N. Komatsu, submitted [4] L. Zhao, A. Shiino, N. Komatsu, J. Nanosci. Nanotechnol. in press

Resume : The silymarin, predominant active principle from the seeds of 'milk thistle' (Silybum marianum L), is a mixture of isomers of flavonolignan nature, which acts as an antioxidant and regulator of the intracellular content of glutathione, cell membrane stabilizer and permeability. The silymarin complex has a low bioavailability because the absorption at gastrointestinal tract level is low. Recently studies shown an improved bioavailability when is encapsulated in biopolymes with synergic actions at gastrointestinal level. In this respect, this study deal with the encapsulation of Silybum marianum L. extract in chitosan nanoparticles to protect against biochemical degradation in gastric environment, and to increase the efficiency of the pharmacological properties, clinical utility, antioxidant and hepatoprotective activity. Spectral characterization and determination of content of silymarin was performed by UV-VIS. The antioxidant properties of the chitosan nanoparticles, Silybum marianum L. extract and of the nano delivery system have been investigated in vitro non cellular by chemiluminescence and DPPH methods. 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. DLS was used to measure the hydrodynamic size and polydispersity index and atomic force microscopy AFM to reveal specific topography of nano-chitosan delivery systems. Keywords: nanochitosan, silymarin, , antioxidant activity, chemiluminescence technique.

Resume : Caenorhabditis elegans (C. elegans) is a 1-mm long free-living soil nematode widely used in biomedicine as a model organism. Its key attributes as an experimental system, including its simplicity, transparency, short life cycle, sequenced genome and small body size, together with the ease of cultivation in the lab, make C. elegans a promising animal model to evaluate nanoparticles in vivo. Our objective is to use C. elegans in the primary screening of nanoparticles with biomedical applications within the manufacturing lab, in order to validate their use, to optimize their design, and to study their toxicity. In the present work, we assessed the stability of the iron oxide nanoparticles (SPIONs) in the C. elegans media by Dynamic Light Scattering. The interaction between SPIONs and C. elegans was evaluated by magnetometry, from which we quantified the iron content of worms treated with different concentrations of SPIONs for 24 hours and evaluated the morphology of SPIONs after this time and excreted SPIONs. The localization of SPIONs within the body of the worm was evaluated using Perls’ Prussian blue staining.

Resume : In this study, we investigated the antioxidant activity of self-assembled biohybrid compounds flavonoid-graphene/graphene oxide (GOX) using chemiluminescence(CL) assay. GOX and graphene are selfassembled with flavonoid compounds (rutin, quercetin, naringin and hesperitin) by activation and co-precipitation in high-density ultrasonic field (~ 260W/cm2 ) in solvent dimethylsulfoxide. The chemiluminescence system for free radicals quenching is generated by the luminol and hydrogen peroxide in an alkaline medium. Graphene shows a very low antioxidant activity by comparison with GOX where dominant are intrinsic functional groups such as –OH, -COOH. Biohybrids based on graphene are not appropriate for the scope as antioxidant support. Biohybrids based on GOX show an improved antioxidant activity. Additional characterizations (AFM, Raman, FT-IR) highlight the contribution of the carboxyl and hydroxyl groups and their interaction with flavonoids to the antioxidant activity. Functionalized graphene and GOX with flavonoids compounds can be used to obtain a new platform to investigate the mechanisms of the free radicals capture. Keywords: Flavonoids, Graphene, Graphene oxide, antioxidant activity, chemiluminescence

Resume : The development of robust, versatile, and high throughput biosensing platforms is expected to have far-reaching implications in medicine, point-of-care clinical diagnostics, pharmaceutical drug development, and genomic and proteomic research. Enabled by rapidly emerging nanoparticles and microfabricated sensor techniques, several new sensing platforms have been proposed and tested for biomedical applications. Biosensing strategies based on magnetic nanoparticles have received considerable attention because they offer unique advantages over other techniques. For example, magnetic nanoparticles are inexpensive to produce, physically and chemically stable, biocompatible, and environmentally safe. In addition, biological samples exhibit virtually no magnetic background, and thus highly sensitive measurements can be performed in turbid or otherwise visually obscured samples without further processing. However to synthesis nano magnetic particle (NMP) with narrow size distribution and high magnetic moment remains the challenges. We report a simple decomposition approach for the synthesis of size-controlled monodispersed magnetite NMPs based on high temperature (265ºC) reaction of Fe(acac)3 in phenyl ether in the presence of alcohol, oleic acid, and oleylamine. With the smaller magnetite NPs as seeds, larger monodispersed magnetite NPs of up to 20 nm in diameter can be synthesized and dispersed into nonpolar solvent by seed-mediated growth method. The process does not require a size-selection procedure and is readily scaled up for mass production. The as-synthesized Fe3O4 nanoparticle assemblies can be transformed easily into c-Fe2O3 NPs by annealing at high temperature (250ºC) and oxygen for 2 h. The synthesized 5, 10 and 20 nm MNP shows excellent magnetic moment with 25, 37 and 45 emu respectively. Those MNPs are well-suitable for bio-molecular labeling and high-sensitive detecting system. 1) Correspondence to zhangw@njut.edu.cn Acknowledgement: National Science Foundation of China under contract 31070883 Jiangsu Province Key Project：Society Development under contract BE2012759

Resume : We report a facile solution-processing approach for producing 3D PEDOT-based micro/nanorod array films, which can be further surface-grafted with capture agents for directed specific recognition to study the cell–substrate interactions on bioelectronics interfaces (BEIs). This BEI platform features the advantageous characteristics: (1) diverse dimensional structures (tunable from the microscale to the nanoscale), (2) varied surface chemical properties (tunable from nonspecific to specific), (3) high electrical conductivity, and (4) reversible chemical redox switching. Furthermore, through systematic studies of PEDOT and PEDOTAc systems, we explore the effects of both chemistry and topography on the circulating tumor cell (CTC)-capture performance. The PEDOTAc-0.4 (400 nm in diameter) surface exhibits the optimal cell-capture efficiency; it could be used to isolate CTCs with minimal contamination from surrounding nontargeted cells (e.g., EpCAM-negative cells, white blood cells) and negligible disruption of the CTCs’ viability and functions. It is conceivable that PEDOT-based micro/nanorod array films function as a critical therapeutic intervention for monitoring tumor progression and metathesis, providing valuable insight into the use of electronics for tissue engineering and regenerative medicine.

Resume : Nanoparticles have gained a significant value in many industrial and medical applications. In 2005 a novel tracer-based imaging method Magnetic Particle Imaging (MPI) has been presented [1], facilitating the direct quantitative detection of the 3D distribution of biocompatible coded superparamagentic iron oxide (SPIO) nanoparticles with high sensitivity, high spatial and high temporal resolution and without any background signal and thus a high signal-to-noise ratio. In this contribution, a quick introduction to the technique of MPI will be presented, highlighting the basic principal of signal generation and reception as well as the hardware setup of state-of-the-art MPI scanners. Furthermore, potential medical imaging applications of MPI and the need of dedicated SPIOs as contrast agents will be discussed. Investigations of e.g. functionalized contrast agents open up further applications beyond cardio-vascular imaging. SPIO optimization in regard to their MPI performance has tremendous potential in increasing the spatial image resolution and image sensitivity. Such optimized SPIOs pave the way towards molecular imaging and cell labeling/tracking. [1] B. Gleich et al., Nature, vol. 435, no. 7046, pp.1214–1217, 2005

Resume : Magnetic polymer networks are a new class of soft polymer materials with properties modulated by magnetic field leading to emerging applications. In this context we elaborated new magnetic sensitive nanocomposite biopolymer-based networks by introducing functionalized magnetic nanoparticles in uncrosslinked aqueous solutions of sodium alginate. Magnetic nanoparticles of maghemite have been synthesized by the polyol process and further functionalized with 3-aminopropyltriethoxysilane bearing NH2 functional groups and able to bind the nanoparticles through the ethoxy groups. The development of a new original device allowed the measurements of mechanical properties under continuous magnetic field [1]. A significant and reversible enhancement of viscoelastic moduli and viscosity at low shear rate has been clearly evidenced [2] and could be explained by intramolecular electrostatic interactions between the positively charged NH3+ groups present at the surface of the magnetic nanoparticles and the negatively charged carboxylate groups (COO-) of sodium alginate chains. This assumption is supported by microscopic observation showing magnetic-induced structures in the nanocomposite materials. [1] (http://www.physique.univ-paris-diderot.fr/magbiomat) [2] A. Ponton, S. Gantz, C. Galindo Gonzalez, L. Ourry, F. Mammeri, S. Ammar-Merah, Elaboration and rheological investigation of magnetic sensitive nanocomposite biopolymer networks, Macromolecules 2014 submitted

Resume : Nanoparticles and their control are of great interest from both academic and industrial points of view, with numerous applications in domains such as medicine, catalysis and material sciences. This talk will stress on metal oxide nanoparticles (NPs) and two main aspects: their use as multifunctionnal contrast agents (CAs) and their potential nanotoxicity. As multifunctionnal CAs, they can provide a multiple targeting and vizualisation of organs or cells with both detectable changes in the MR and optical signals intensity of the target. A second aspect of the NPS world is their nanotoxicology which has attracted the attention of public authorities worldwide. The established methods of chemical safety assessments have to be modified to address the special characteristics of NPs and more especially to assess their biological effects. There is an urgent need to evaluate the risks of these particles to ensure their safe production, handling, use, and disposal. In particular, the behavior of nanoparticles inside living cells is still an enigma, and no metabolic responses induced by these particles are understood so far. With this respect, we have examined the potential toxicity due to exposure of TiO2 NPs used in sunscreens and cosmetics. We applied an original multimodal imaging methodology (Ion Beam Analysis, TEM, & Confocal microscopy) to in vitro and in vivo studies, combining technologies for, tracking, quantification of TiO2 nanoparticles as well as the use of indicators for ion homeostasis, cell metabolism, or cell fate. Our main goal is to precisely identify the molecular and cellular mechanisms involved in the nanotoxicity of TiO2 nanoparticles in eukaryotic cells and in multi-cellular organisms such as Caenorhabditis elegans (C. elegans).

Resume : In this work we present an alternative method to fabricate contamination-free, functional complex inorganic-organic nanohybrid materials (DNA and protein-labelled nanoparticles) in very high quantities within seconds in a single-step process using picosecond-pulsed laser ablation with in-situ bioconjugation. Use of picosecond laser pulses demonstrates a significantly higher efficiency than existing laser technologies. Structure integrity of conjugated biomolecules demonstrates that nearly 100% entire nanobiohybrids can be reached under controlled conditions. Functionality tests of the nanobiohybrids are proven by immunoblotting and cellular immunolabeling, resulting in enhanced cytoskeleton staining than that achieved using conventional labeling markers. The effects of nanoparticle photo-fragmentation and heat transfer from photo-excited nanoparticles to the surrounded biomolecules are (bio)physically considered and explained. We also present detailed information about nanomaterial surface characteristics and biomolecule binding formation and give deep insights into the physical interaction of the laser beam with the biomolecules and nanoparticles. Accent is put on biomolecule structure integrity and bioactivity by highlighting physical processes occurring that might cause biomolecule denaturation. The work covers the topics of laser physics, material science, engineering, chemical analytics, biomedical diagnostics and shows the first working laser-based immunoassays.

Resume : Cellulose from microbial origin, commonly known as bacterial cellulose (BC), is becoming a commodity material since it incorporates desirable structural properties for biomedical applications. Here, we present the production and characterization of bacterial cellulose (BC) films of less than a hundred microns thick produced by Glucoacetobacter bacteria. These thin films are processed using three different drying methods: 1) room temperature, 2) freeze drying and 3) supercritical drying. The different processes confer to the cellulose films a hierarchical porous network, high purity and crystallinity, flexibility and strength (high Young modulus at room and elevated temperatures) and large water holding capacity that can be tailored and controlled for different applications. In this work, we used BC films as platform to incorporate magnetic functionality by the incorporation of iron oxide nanoparticles. Using the microwave-assisted method in a rapid and cost effectively manner, we magnetically coated the whole structure of our BC films. Evaluation of different precursor´s concentrations and taking advantage of the different drying methods we achieved magnetic bacterial films with different magnetic strength. We obtained magnetic BC composites flexible, robust and with high magnetization within few minutes in a clean, easy and reproducible method. In the talk, we would illustrate the synthesis and characterization of the magnetic BC films as well as the flexible and magnetic properties achieved.

Resume : A facile approach for forming organic-inorganic hybrid hollow capsules driven by the self-assembly of amphiphilic block codendrimers is described. The block codendrimers were designed to consist of a central Y-shaped aromatic core at which hydrophilic and hydrophobic dendrons were attached, and synthesized using azide-alkyne click chemistry. The block codendrimer with longer dodecyl chains (falkyl/EO=1.28) self-assembled into supramolecular vesicles with a bilayer membrane in water but formed spherical micelles in n-hexane. A decrease in the alkyl chain length to heptyl (falkyl/EO=0.89) arranged the codendrimers into vesicular assemblies in both hydrophilic and hydrophobic solvents. The propensity of the dendritic amphiphiles to form vesicles with a bilayer shell allowed the incorporation of inorganic nanoparticles in the membrane interior. Indeed, hydrophobically and hydrophilically modified quantum dots (QDs) were successfully entrapped within the wall of vesicles in water and n-hexane, respectively, through a simple self-assembly process without any structural disruption. However, the presence of an inner cavity of the hybrid vesicles encapsulated another type of QD to be well-dispersed in solvent environments. Consequently, the inorganic nanoparticle-loaded vesicles in this study open up a new perspective for elaborate engineering of the electro-optical properties of nanomaterials and efficient transporting of chemical species as a model system in designing multifunctional nanocarriers.

Resume : Nanoparticles combining optical and magnetic signals for detection by hand-held probes are promising for the detection of sentinel nodes in cancer surgery. Now, radioactive colloids (RuS labelled with 99mTc) or/and Vital Blue dye are injected around the primary tumour and detected by nuclear probe or the eye respectively. The aim of our work is to replace the radioactive colloids by a an optomagnetic marker. Thus, we have developed and optimized dendronized iron oxide nanoparticles, with dendrons that can be of first or second generation and bear a Patent Blue dye and/or a fluorescent dye. Aqueous suspensions of our nanoparticles have been characterized for size, magnetic susceptibility and the amount of incorporated Patent Blue/fluorescent dye. We show that the structure and the composition of the aggregates strongly impact the optical and magnetic properties of the suspensions and therefore are critical for optimizing their detection sensitivity. Major attention was given to the effect of the dendron length, the grafting ratios, as well as to the electrostatic interactions between the dendron and the dye. Finally, in-vivo experiments on rats have been performed to determine biodistribution and to assess the detection sensitivity our optomagnetic marker nanoparticles. Acknowledgments This work was supported by the European Union in the framework of the program «Nano@matrix» INTERREG IV Upper Rhine Valley.

Resume : Stimuli responsive materials (SRM) have been of special interest for the last two decades, due to their ability to respond to the external stimuli such as temperature and pH. Therefore, SRM represent one of the most significant and emerging field of scientific interest with wide range of promising applications. In this study we demonstrate the synthesis of temperature activated polymeric nanotubes of Poly(N-isopropylacrylamide) (PNIPAAM) hydrogel. The PNIPAAM hydrogels belong to the group of ‘‘smart’’ materials that undergo a temperature-induced phase transition at a critical temperature (Tc) related to the lower critical solution temperature (LCST). The nanotubes are fabricated by conformally coating the pores of anodic aluminium oxide membranes with stimuli responsive polymers using initiated chemical vapor deposition. The physical and morphological properties of nanotubes are studied using various characterization tools such as FTIR, Raman, Ellipsometer and SEM. Furthermore, We report the results of our studies on the loading and unloading kinetics of Phloroglucinol (PhG) dye through thermoresponsive nanotubes. PNIPAAM hydrogels have an LCST in aqueous medium around 32–34°C which is close to the human body temperature. Thus, work presented here demonstrates the great scope of the thermo responsive nanostructures in the field of drug delivery potential application.

Resume : Bio-molecular detecting arrays have been successfully implemented in a variety of applications ranging from genome-wide screens for chromosomal abnormalities to the identification of coregulated gene networks during embryonic development. However, while gene function studies that utilize mRNA expression levels are somewhat informative, they often do not correspond well with the abundance of protein levels in the cell. Accordingly, many researchers have adopted protein microarrays to directly investigate protein expression patterns and protein function. Protein microarrays make it possible to study the expression of the entire proteome (or a subset of the proteome) in a multiplex format. Although this advance addresses a crucial limitation, protein microarrays have enjoyed limited success thus far compared to DNA microarrays due to the highly complex nature of the antibody-antigen interaction. We report a novel nanosensor-based technique that can simplify and enhance the reliability of protein array-based analysis, allowing the field to unlock the true potential of protein microarrays. we have designed a simple and sensitive nanosensor-based immunoassay capable of rapidly characterizing antibody cross-reactivity. This assay employs high density arrays of Spin tunneling magnetoresistive (TMR) nanosensors and magnetic nanotags. The sensitivity of TMR system is two folds higher than giant magnetoresistance (GMR), which currently developed by many other groups. This assay utilizes as a one-step, wash-free process employing the site-specific autoassembly characteristics of macromolecular complexes. The sensor can successfully detect CEA marker at pL level. 1) Correspondence to zhangw@njut.edu.cn Acknowledgement: National Science Foundation of China under contract 31070883 Jiangsu Province Key Project：Society Development under contract BE2012759

Resume : We report the development of a well-defined stem cell culture system using surface functionalized polymeric nanopillars with tunable surface chemical and physical properties. Nanopillars, modified with peptides derived from vitronectin, can be used as defined substrates to maintain both human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells for up to 3 months without differentiation. The surface chemical properties of the nanopillars were more critical than the physical properties in maintaining stem cells. However, the physical properties of the Nanopillars influenced the stem cell fate. Softer Nanopillars promoted the undifferentiated state, and more rigid Nanopillars encouraged stem cell differentiation.

Resume : In the last decade, design of the biohybrid materials has gained a considerable interest in the nanotechnological field. This paper described an original design of bionanoarchitectures with interesting properties and potential bio-applications. Multilamellar lipid vesicles (MLVs) with and without cholesterol, obtained by thin film hydration method were labelled with chlorophyll a (Chla) as a sensor to detect any modifications in the artificial lipid bilayers. These biomimetic membranes were used to build noncovalent structures with single-walled carbon nanotubes. Different biophysical methods were employed to characterize these biohybrids: UV-VIS absorption and emission spectroscopy, DLS, AFM, chemiluminescence technique. The designed nanobioarchitectures exhibited good physical stability, high antioxidant and antimicrobial properties and could be used as biocoating materials.

Resume : Water soluble gold nanoparticles (GNPs) own physical and chemical properties with a large scope of application in the biomedical research. Our project aims to develop new synthetic pathways for the direct synthesis of GNPs already possessing functionality allowing easy access to bio functionalization. This is achieved by using synthesized water soluble molecules. These molecules are bifunctional : One functional group is able to both reduce gold(III) chloride and to coat the surface of the obtained GNPs. The other functional group will remain inert during the NPs synthesis and will allow further chemoselective GNPs functionalization. Herein we will present the mechanism of this GNPs synthesis. We have demonstrated the related mechanism of this colloid formation and the interaction between our bifunctional molecules and the gold surface by classical analytical chemistry techniques. Optimization of the various synthesis parameters (temperature, concentration and pH) have been assessed to yield homogeneous GNPs of size ranging from 13-21 nm. Then reactions at the surface with the remaining, functional group have been characterized, confirming their chemoselective reactivity. These new GNPs are also used as a building block for sized controlled covalent assemblies preparation. The controlled size assemblies are water soluble and presents specific optical properties shifting from blue to NIR absorption yielding to promising in vivo applications such as hyperthermia.

Resume : Metallic artificial implants are widely used as medical devices to replace, support or enhance an existing biological structure. Most of them are made of titanium or its alloys due to their advanced mechanical properties and excellent biocompatibility. The essential requirement is to possess not only biocompatibility, but also bioactivity with the host. We propose an alternative technique for coating Ti-6Al-4V with calcium phosphate. The composition of the metal surface is modified by a chemical reaction in an alkaline media, and then coated by a Ca-P layer using a ?chimie douce? method. This new deposition route has several advantages such as controlled conditions, applicability to complex shapes, no adverse effect of heating, and cost effectiveness. The coating has been characterized by X-ray diffraction, scanning electron microscopy performed on transverse section, and EDSX analysis. No delamination was observed under ?scratch? tests. These experimental treatments allowed producing cytocompatible materials potentially applicable to manufacture implantable devices for orthopaedic and oral surgeries.

Resume : Gold-coated palladium nanoparticles (Pd@Au NPs) were synthesized for prostate cancer brachytherapy, which is the most diagnosed cancer among men today in the western world. In fact, currently available brachytherapy procedures rely on injections of low-dose millimetric (4-5mm) radioisotope seeds such as 103Pd. Because these seeds are relatively large, it is difficult to irradiate the tumors uniformly; such size also causes discomfort and inflammation to patients. In this research project, we aim to investigate the potential of 103Pd@Au NPs microinjections (1-5 microL) to control the growth of prostate cancer tumors. To achieve this, a new and rapid protocol enabling the synthesis of Pd NPs coated with a Au shell conferring enhanced biocompatibility, Pd core stability and radiosensitization potential (to enhanced treatment by 103Pd irradiation) was developed. The synthesis is based on wet chemical reduction, and Pd@Au NPs size obtained was found to be 40 nm in average (TEM). To enhance colloidal stability, poly (ethylene glycol) was grafted at the surface of the NPs. These NPs were then characterised by UV-Vis, DLS, XPS and FTIR. Pd@Au NPs were injected in vivo in a prostate cancer tumor model, and the tumors were imaged in vivo using computed tomography (CT). The site of NPs injection was clearly identified by imaging and could facilitate dosimetric calculations that are necessary to better plan and refine radioactive nanoparticles-based brachytherapy procedures.