Over the last few decades, nanoparticles have been studied in theranostic field with the objective of exhibiting a long circulation time through the body coupled to major accumulation in tumor tissues, rapid elimination, therapeutic potential and contrast properties. In this context, we developed sub-5 nm gadolinium-based nanoparticles that possess in vitro efficient radiosensitizing effects at moderate concentration when incubated with head and neck squamous cell carcinoma cells (SQ20B). Two main cellular internalization mechanisms were evidenced and quantified: passive diffusion and macropinocytosis. Whereas the amount of particles internalized by passive diffusion is not sufficient to induce in vitro a significant radiosensitizing effect, the cellular uptake by macropinocytosis leads to a successful radiotherapy in a limited range of particles incubation concentration. Macropinocytosis processes in two steps: formation of agglomerates at vicinity of the cell followed by their collect via the lamellipodia (i.e. the "arms") of the cell. The first step is strongly dependent on the physicochemical characteristics of the particles, especially their zeta potential that determines the size of the agglomerates and their distance from the cell. These results should permit to control the quantity of particles internalized in the cell cytoplasm, promising ambitious opportunities towards a particle-assisted radiotherapy using lower radiation doses.

Buchnera aphidicola is an obligate symbiotic bacterium that sustains the physiology of aphids by complementing their exclusive phloem sap diet. In this study, we reappraised the transport function of different Buchnera strains, from the aphids Acyrthosiphon pisum, Schizaphis graminum, Baizongia pistaciae and Cinara cedri, using the re-annotation of their transmembrane proteins coupled with an exploration of their metabolic networks. Although metabolic analyses revealed high interdependencies between the host and the bacteria, we demonstrate here that transport in Buchnera is assured by low transporter diversity, when compared to free-living bacteria, being mostly based on a few general transporters, some of which probably have lost their substrate specificity. Moreover, in the four strains studied, an astonishing lack of inner-membrane importers was observed. In Buchnera, the transport function has been shaped by the distinct selective constraints occurring in the Aphididae lineages. Buchnera from A. pisum and S. graminum have a three-membraned system and similar sets of transporters corresponding to most compound classes. Transmission electronic microscopic observations and confocal microscopic analysis of intracellular pH fields revealed that Buchnera does not show any of the typical structures and properties observed in integrated organelles. Buchnera from B. pistaciae seem to possess a unique double membrane system and has, accordingly, lost all of its outer-membrane integral proteins. Lastly, Buchnera from C. cedri revealed an extremely poor repertoire of transporters, with almost no ATP-driven active transport left, despite the clear persistence of the ancestral three-membraned system.

Sugar moieties play a prominent role in a myriad of biological processes, which explains the latest development of glycomimetics to simulate the attributes of naturally occurring oligo-or polysaccharides.1 Monosaccharides generally weakly interact with their receptors, whereas several epitopes grafted on a common scaffold (multivalent molecules, dendrimers, polymer chains) show enhanced activities -thanks to the cluster glycoside effect -for targeting specific glycan-binding proteins. Recently, we demonstrated that a careful establishment and reading of both oil and polymer phase diagrams allows for setting conditions ensuring the rapid preparation of nanocapsules in a simple batch mixing. 7 This concomitant nanoprecipitation/polymer crosslinking procedure (called ''Shift'N'Go process'') also permits simultaneous functionalization of the shell and filling of the core with molecules of biological interest. In this communication, we substantiate this proof of concept by preparing biocompatible functional capsules of utility for bio-applications. Particularly, we report on the one-pot synthesis of precisely defined, miglyol-filled, epoxide-functionalized glyconanocapsules and on subsequent post-modifications of the polymer shell via ring opening reactions. We show that the nanocapsules can be easily loaded with actives and that the presence of numerous pendent epoxides within the walls permits an efficient incorporation of relevant molecules such as ligands, probes or metal nanoparticles. Furthermore, the multiple n-heptyl a-D-mannose motifs present at the capsule surface strongly interact with the lectin sugarbinding sites (adhesin FimH) of adhesive proteinaceous hair-like organelles (type 1 fimbrae) expressed by Escherichia coli (E. coli) to promote adhesion and infection of tissues. 8 The construction of tag-labelled nanocapsules, with bright fluorophores and/or coated magnetic nanoparticles, is exploited here to monitor aggregation kinetics between the mannosylated nano-objects and AdherentInvasive E. coli bacteria (AIEC) and promote bacterial removal. A water-soluble random copolymer of N-[7-(a-D-mannopyranosyloxy)heptyl] methacrylamide (HMM) and glycidyl methacrylate (GMA) was prepared by 4-cyano-4-(phenylcarbonothioylthio) pentanoic acid-mediated RAFT polymerization (P(HMM 206 -stat-GMA 17 ), M n NMR = 77.1 kg mol À1, Ð = 1.10, details in ESI †). In order to account for the disparity between the relative reactivity ratios of the two monomers (r GMA = 2.82/2.77 and r HMM = 0.14/0.13 using Jaacks and Kelen-Tüdös methods, respectively, see ESI †) and the hydrophobicity of GMA, polymerizations were carried out in a semi-batch process using a low molar fraction of GMA (see Experimental part

Alkyne-functionalized cellulose fibers have been generated through etherification under basic water or hydroalcoholic conditions (NaOH/H(2)O/isopropanol). For a given NaOH content, the medium of reaction and, more particularly, the water/IPA ratio, were shown to be of crucial importance to derivatize the fibers without altering their integrity and their crystalline nature. It was shown that the degree of substitution (DS) of the fibers increases concomitantly with isopropanol weight ratio and that, contrary to water or water-rich conditions, derivatization of fibers under isopropanol-rich conditions induces an alteration of the fibers. Optimization of etherification conditions in aqueous media afforded functionalized cellulose materials with DS up to 0.20. Raman confocal microscopy on derivatized fibers cross sections stressed that alkyne moieties are incorporated all over the fibers. The resulting fibers were postfunctionalized by molecular probes and macromolecules in aqueous or water-rich conditions. The effectiveness of the grafting was strongly impacted by the nature of the coupling agents.

Chitosan-based hydrogels displayed promising in vitro biocompatibility and hemocompatibility properties as well as in vivo short-term performance.