Contribution of cobalt-mediated radical polymerization to macromolecular engineering and photodynamic therapy

Cobalt-mediated radical polymerization (CMRP) is an emerging class of controlled radical polymerization technique based on the reversible deactivation of the propagating radicals by a cobalt complex. This thesis aims at broadening the nature, the structure, the properties and the end-use of (co)polymers accessible by CMRP. The first part of this work is devoted to the synthesis of novel statistical, graft and block copolymers by CMRP. First, the statistical copolymerization of conjugated (n-butyl acrylate) with a non-conjugated one (vinyl acetate) has been successfully controlled by bis(acetylacetonato)cobalt(II). The optimal experimental conditions were then implemented to the copolymerization of vinyl acetate with poly(ethylene glycol) acrylate, which yielded (quasi-)diblock amphiphilic graft copolymers for potential biomedical applications in one step. CMRP also revealed successful for the synthesis of well-defined thermo-responsive copolymers based on poly(N-vinylcaprolactam), either amphiphilic or double-hydrophilic at room temperature. In the second part of this thesis, we investigated the potential of CMRP for the synthesis of new agents for cancer photodynamic therapy. The synthesis of such photosensitizers relied on the chain-end functionalization by [60]fullerene of water-soluble (co)polymers (or precursors) prepared by CMRP. The photodynamic activity of poly(vinyl alcohol)/C60, poly(N-vinylpyrrolidone-co-vinyl acetate)/C60 and poly(PEG acrylate-co-vinyl acetate)/C60 nanohybrids were assessed through photophysical and in vitro experiments. Also, the ability of the nanohybrids to avoid recognition by the immune system was evaluated by a protein adsorption test. Finally, some hints on how to improve the synthesis of the nanohybrids - and therefore, their photodynamic activity - were provided by a mechanistic study of the grafting onto C60 of macroradicals released by cobalt end-capped polymers