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Biocompatible Polyion Complex Micelles Synthesized from Arborescent Polymers

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journal contribution
posted on 22.11.2016, 00:00 by Vo Thu An Nguyen, Marie-Claire De Pauw-Gillet, Olivier Sandre, Mario Gauthier
Water-dispersible polyion complex (PIC) micelles were prepared by the self-assembly of an arborescent polystyrene-graft-poly­(2-vinylpyridine) copolymer (denoted G0PS-g-P2VP or G1) serving as core and a poly­(acrylic acid)-block-poly­(2-hydroxyethyl acrylate) (PAA-b-PHEA) double-hydrophilic block copolymer (DHBC) forming a shell. Varying the density of hydrophilic polymer chains in the stabilizing layer provided control over the size and structure of the entities obtained, from large flocculated species to stable isolated PIC micelles with diameters ranging from 42 to 67 nm. The hydrodynamic radius (determined from dynamic light scattering measurements), and the weight-average molar mass (w) and radius of gyration of the scatterers (extracted from static multiangle light scattering data) evidenced the formation of either isolated or aggregated PIC micelles depending on the self-assembly conditions used (pH, concentration and mixing molar ratio f). Changes in the morphology of the arborescent copolymer after complexation were observed by atomic force microscopy (AFM) imaging. In particular, by varying the force applied with the AFM tip on the samples, the core–shell structure of the PIC micelles was clearly evidenced. The PIC micelles displayed no significant cytotoxicity toward mouse fibroblast L929 cells, a standard cell line recommended for toxicity assays, due to the good biocompatibility of the hydrophilic PAA-b-PHEA shell. In spite of a negative residual zeta potential due to an excess of negative charges, fluorescently labeled PIC* micelles were successfully internalized by L929 cells, as confirmed by laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM).

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