Synthesis of dextran-based chain transfer agent for RAFT-mediated polymerization and glyco-nanoobjects formulation.

Glycopolymers based on dextran are frequently prepared via ATRP, whereas the use of RAFT polymerization is strangely limited due to the difficult synthesis of Dextran-based macromolecular chain transfer agent (DexCTA). The aim of this work is to establish a controlled and reproducible methodology for its preparation. Direct esterification of the hydroxyl dextran functions is the most common method. Our study shows that this latter leads to a very low degree of functionalization. As alternative, we report a reproductible multistep strategy consisting of oxidation, amination, and amidation reactions. Various DexCTAs with tunable degree of substitution (respectively 0.025, 0.045, and 0.06) were successfully prepared. As proof of concept, one of the DexCTAs was involved in the photo-mediated RAFT polymerization of hydroxypropyl methacrylate in DMSO to prepare amphiphilic Dex-g-PHPMA glycopolymers, which can self-assemble in water into monodisperse spherical nano-objects. MTT assays revealed the biocompatibility of all dextran derivatives.

Mixing Block Copolymers with Phospholipids at the Nanoscale: From Hybrid Polymer/Lipid Wormlike Micelles to Vesicles Presenting Lipid Nanodomains.

Hybrids, i.e., intimately mixed polymer/phospholipid vesicles, can potentially marry in a single membrane the best characteristics of the two separate components. The ability of amphiphilic copolymers and phospholipids to self-assemble into hybrid membranes has been studied until now on the submicrometer scale using optical microscopy on giant hybrid unilamellar vesicles (GHUVs), but limited information is available on large hybrid unilamellar vesicles (LHUVs). In this work, copolymers based on poly(dimethylsiloxane) and poly(ethylene oxide) with different molar masses and architectures (graft, triblock) were associated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Classical protocols of LUV formation were used to obtain nanosized self-assembled structures. Using small-angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM), we show that copolymer architecture and molar mass have direct influences on the formation of hybrid nanostructures that can range from wormlike hybrid micelles to hybrid vesicles presenting small lipid nanodomains.