Recent insights in magnetic hyperthermia: From the “hot-spot” effect for local delivery to combined magneto-photo-thermia using magneto-plasmonic hybrids

International audienceMagnetic hyperthermia which exploits the heat generated by magnetic nanoparticles (MNPs) when exposed to an alternative magnetic field (AMF) is now in clinical trials for the treatment of cancers. However, this thermal therapy requires a high amount of MNPs in the tumor to be efficient. On the contrary the hot spot local effect refers to the use of specific temperature profile at the vicinity of nanoparticles for heating with minor to no long-range effect. This magneto-thermal effect can be exploited as a relevant external stimulus to temporally and spatially trigger drug release.In this review, we focus on recent advances in magnetic hyperthermia. Indirect experimental proofs of the local temperature increase are first discussed leading to a good estimation of the temperature at the surface (from 0.5 to 6 nm) of superparamagnetic NPs. Then we highlight recent studies illustrating the hot-spot effect for drug- release. Finally, we present another recent strategy to enhance the efficacity of thermal treatment by combining photothermal therapy with magnetic hyperthermia mediated by magneto-plasmonic nanoplatforms

Dévelopment of nano-catalysts for C-C cross coupling reactions

Ces dernières années, l’intérêt porté à l'obtention de nouveaux systèmes catalytiques a connu un essor fulgurant. Ceci est lié, en particulier, aux applications industrielles variées qui s'étendent de la chimie fine à la chimie pharmaceutique. De nombreux catalyseurs ont ainsi été développés pour un nombre toujours croissant de réactions organiques. Néanmoins, la plupart des catalyseurs homogènes sont difficiles à adapter aux procédés industriels du fait de problèmes de séparation et de régénération. De plus, même efficaces, la plupart des catalyseurs contiennent des métaux nobles, coûteux et difficiles à recycler. C’est pourquoi, de nouveaux protocoles plus économiques et plus respectueux de l’environnement ont besoin d’être recherchés. L’utilisation de nanoparticules magnétiques comme support catalytique en synthèse organique représente une solution innovante pour répondre aux problèmes catalytiques rencontrés. Le but de ce travail consiste à concevoir des nano-catalyseurs magnétiques et à évaluer leur activité catalytique ainsi que leur recyclage pour des réactions de couplage carbone-carbone très utilisées en synthèse organique. Des nanoparticules de Maghémite synthétisées dans en milieux aqueux sont ensuite stabilisées en surface par des agents complexants possédant une fonction terminale qui permettra de les fonctionnaliser avec le catalyseur désiré (L- Proline, peptides, alcaloïde, Palladium). Ces nanomatériaux hybrides, constitués d'un cœur inorganique et d'une couche organique, ont été caractérisés par diverses techniques afin de déterminer leurs propriétés. Leurs activités ont été évaluées sur des réactions de couplage carbone-carbone modèles d'aldolisation, d'addition 1,4 de Michael et la réaction de Suzuki-Miyaura.In the last decades, the interest for new catalysts and new catalytic reactions dramatically increased due to their miscellaneous industrial applications in fine or pharmaceutical chemistry for example. Lots of catalysts have been developed for an increasing number of organic reactions. Nevertheless, most of homogeneous catalysts are difficult to adapt to industrial process due to separation and regeneration problems. Furthermore, even if they are highly efficient, most of the catalysts contain noble metals often expensive and difficult to recycle. That’s why greener and much more economic protocols need to be developed. The use of nanoparticles as solid support for catalysts in organic chemistry appears as an innovative solution for solving these problems. Among the different inorganic nanomaterials, iron oxide nanoparticles represent an attractive tool due to their magnetic properties and easiness of obtaining. The aim of these work consist in designing magnetic nanocatalysts and evaluating their catalytically activity and recycling in C-C bond formation reactions which are commonly used in organic chemistry. Iron oxide nanoparticles (γ-Fe₂O₃) have been synthesized by soft chemistry in aqueous media. Particles have then been stabilized on surface by bidendate coating agents bearing a terminal function which enables post functionnalization with the desired catalyst (L-Proline, peptides, alkaloid, Palladium). These hybrids nanomaterials, with an inorganic core and an organic shell, have been characterized with various techniques in order to determine their properties. Catalysts activities have been evaluated on model C-C bond formation reactions such as aldolisation, 1, 4-Michael addition and cross coupling Suzuki-Miyaura cross coupling

Nano-organocatalysts synthesis: Boc vs Fmoc protection

International audienceWe report the elaboration of new l-Proline functionalized superparamagnetic iron oxide nanoparticles that can act as a new enantioselective organocatalyst. Boc-l-Proline and Fmoc-l-Proline are grafted using two different methodologies on a nanoplateform constituted of 10 nm maghemite (γ-Fe2O3) nanoparticle stabilized by bidendate coating agent Alendronate. We show that coupling is far more efficient using microwave assisted methodology and that only Fmoc deprotection is compatible with our nanoplatform. Moreover the fluorenyl group is used for indirect quantification of grafted Proline onto nanoparticles

Microwave Assisted Functionalization of Materials: from the Mesoscale to the Nanoscale

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Nanoparticles under the light: click functionalization by photochemical thiol-yne reaction, towards double click functionalization.

International audienceA light click away: The first application of the thiol-yne reaction to nanoparticle functionalization is described (see figure). This metal-free click chemistry approach is compatible with the addition of various molecules at the surface and can be combined with CuAAC methodology to perform chemoselective double functionalization

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

International audienceNanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the EWS-FLI1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-FLI1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA

Using hydrogen isotope incorporation as a tool to unravel the surfaces of hydrogen-treated nanodiamonds

International audienceWe report here on a robust and easy-to-implement method for the labelling of detonation nanodiamonds (DND) with hydrogen isotopes (deuterium and tritium), using thermal annealing performed $in\ a\ closed\ system$. With this method, we have synthesized and fully characterized (FTIR, Raman, DLS, $^3$H/$^2$H/$^1$H and $^{13}$C MAS NMR) deuterium-treated and tritium-treated DND and demonstrated the usefulness of isotope incorporation in investigating the surface chemistry of such nanomaterials. For instance, surface treatment with deuterium coupled to FTIR spectroscopy allowed us to discriminate the origin of C–H terminations at the DND surface after the hydrogenation process. As a complementary, tritium appeared very useful for quantification purposes, while $^{1,2,3}$H NMR confirmed the nature of the C–$^{1,2,3}$H bonds created. This isotopic study provides new insights into the characteristics of hydrogen-treated DND