Fonctionnalisation et transformation de nanoparticules et leur application biomédicale

L’objectif primordial a été le développement de stratégies de fonctionnalisation de surface polyvalente pour différentes nanoparticules notamment de nanoparticules de diamant, les nanostructures en or et ses nanocomposites. Un objectif particulier a été l'utilisation du graphène oxide réduite et des nanostructures en or pour l'ablation photo-thermique ou photo-dynamique des pathogènes.Incorporation de la vertéporfine, un photo-sensibiliteur cliniquement approuvé, sur des nanostructures en a permis une éradication efficace d'une souche virulente de E. coli associé à une infection des voies urinaires. L’utilisation du graphène oxide reduite,lorsqu'il est éclairé avec un laser infrarouge proche, a permis une destruction photothermique de la même souche de E. coli.En parallèle, l'intérêt d'utiliser des nanoparticules de diamant (NDs) modifié avec le menthol ainsi que différents sucres comme agent antibactérien contre les bactéries Gram-positif (Staphylococcus aureus) et Gram négatif (Escherichia coli) a été montré. Une stratégie pour l’intégration covalente des sucres, en tirant profit de la photochimie de arylazides, a été développée en parallèle. Le nitrène, une intermédiaire très réactif, est censé interagir avec des glycanes en créant des liaisons covalentes très robustes. Les glyco- NDs ainsi formés ont maintenu leur affinité envers des lectines. Grâce à un test d'agglutination à la base de fluorescence nous avons montré que les particules mannan-NDs montrent un effet d’agglutination des E. coli à des concentrations de ≈10 pg ml - 1, étant beaucoup plus faible que le mannan libre et mannose-NDs.The primal focus of the research work was the development of versatile surface functionalization strategies for different nanoparticles ranging from diamond nanostructures to gold nanorods and nanocomposites. One particular aim was the use of reduced grpahene oxide (rGO) and silica coated gold nanorods for the photothermal and photodynamic ablation of pathogens. Embedding of verteporfin, a clinically approved photosensitizer, into silica-coated gold nanorods allowed an efficient eradicaiton of a virulent strain of E. coli associated with urinary tract infection. The great heating effect of graphene-coated gold nanorods when illuminated with a near-infrared laser allowed for a photothermal destruction of the same pathogenic strain. In parallel, we have shown the interest of using diamond nanoparticles (NDs) modified with menthol as well as different sugars as antibacterial agent against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia Coli) bacteria. We developed a strategy for the covalent attachment of sugars by taking advantage of the photochemistry of arylazides, which upon light activation convert to reactive nitrenes. The highly reactive nitrene intermediate formed is believed to interact with glycans through C-H and N-H insertion reactions, creating highly robust covalent linkages. The resulting glyco-NDs maintained their expected binging affinity and specificity towards their partner lectins. Through a fluorescent based agglutination assay, we showed that mannan-NDs display E. coli agglutination at concentrations of ≈10 µg mL-1, being much lower than free mannan and mannose-NDs

Plasmonic photothermal cancer therapy with gold nanorods/reduced graphene oxide core/shell nanocomposites

International audienceGold nanorods (Au NRs) are known for their efficient conversion of photon energy into heat, resulting in hyperthermia and suppression of tumor growth in vitro and in vivo. Au NRs are thus of great promise for photothermal therapy (PTT) of different cancers. From the point of cancer therapy, low laser powers are essential (≤1 W cm −2) to ensure minimal side effects such as skin burning. Herein, we investigate the potential of polyethylene glycol functionalized reduced graphene oxide (rGO-PEG) enrobed Au NRs for the photothermal destruction of human glioblastoma astrocytoma (U87MG) cells in mice. We show that Au NRs@rGO-PEG are ideal multifunctional theranostic nanostructures that can exert efficient photothermal destruction of tumors in mice upon low doses of NIR light excitation and can act as fluorescent cellular markers due to the presence of a NIR dye integrated onto the rGO shell. Due to the specific interaction between Tat protein modified Au NRs@rGO-PEG nanostructures with the human glioblastoma astrocytoma (U87MG) cells, selective targeting of the tumor is achieved. In vivo experiments in mice show that upon irradiation of the tumor implanted in mice at 800 nm under low doses (0.7 W cm −2), U87MG tumor growth gets suppressed. The study demonstrates that the novel nanomaterials allow for an efficient destruction of solid tumors and might thus serve as an excellent multi-functional theranostic agent in photothermal therapeutic applications

Mathematical modelling of filtration processes in drainage systems with different depths of drainage

The article discusses the option for the application of the methodology for the solution of boundary value problems on the conformal mapping for the calculation of filtration process in the horizontal systematic drainage, provided that the drain is installed at a different depth. In particular, the case of methods combining fictitious areas and quasiconformal mappings for solving nonlinear boundary conditions problems for calculating filtration regimes in soils with free sections of boundaries (depression curves) and intervals of the “drainage” type. As an example, the authors designed a hydrodynamic flow grid, determined the values of the flows to the drain, established a section line and elicited other process characteristics. The algorithm for the numerical solution of model nonlinear boundary conditions problems of quasiconformal reflection in areas bounded by two equipotential lines and two flow lines, when for one of the sections, the boundary is an unknown (free) curve with fixed and free ends. The conducted numerical calculations prove that the problems and algorithms of their numerical solution, with a relatively small iterations number (k = 141) suggested in the paper, can be applied in the simulation of nonlinear filtration processes that arise in horizontal drainage systems. Total filtration flow obtained Q = 0.9 dm3∙s–1; flow for drains Q1 = 0.55 dm3∙s–1 and Q2 = 0.35 dm3∙s–1 are quite consistent with practically determined values