Biocompatible Polyion Complex Micelles Synthesized from Arborescent Polymers

Abstract

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 (M̅) 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).

Magnetic Polyion Complex Micelles for Cell Toxicity Induced by Radiofrequency Magnetic Field Hyperthermia

“…The G1 or G0PS- g -P2VP copolymer (M¯n = 1.1 × 10 6 g·mol −1 ; M¯w/M¯n = 1.08) was synthesized by Gauthier et al [12] by anionic polymerization and grafting. The preparation of double-hydrophilic block copolymers (DHBC) PAA 13 - b -PHEA 150 (M¯w/M¯n = 1.23), PAA 27 - b -PHEA 260 (M¯w/M¯n = 1.16) and the fluorescently labelled derivative PAA 27 *- b -PHEA 260 was achieved by atom-transfer radical polymerization (ATRP) of the corresponding protected monomers ( tert -butyl acrylate and 2-trimethylsilyloxyethyl acrylate, respectively) as described previously [27] and carbodiimide hydrochloride (EDC) activated amide bond formation with fluoresceinamine (ESI-S2).…”

“…Considering the composition of the arborescent copolymer G0PS- g -P2VP (or in short G1) used as template for MNP synthesis, whose 2VP units can be protonated, a polymer stabilizing shell bound through polyelectrolyte complexation already reported for copolymer micelles [26] appears promising, as it offers stronger interactions rather than mere physical adsorption and is much more versatile than covalent bonding. In this article, the polyion complexation process of G1 unimolecular micelles with PAA- b -PHEA DHBC chains was adapted from our previous study [27] to produce MPIC micelles, noted G1@Fe 3 O 4 , containing MNPs synthesized in situ by a templated coprecipitation route. The colloidal stability of MPIC micelles at pH 7 was studied by dynamic light scattering (DLS), while their morphology was observed by atomic force microscopy (AFM) imaging.…”

Nanodrug Delivery Systems for the Treatment of Ovarian Cancer

“…This method is used in insoluble polymers, including Pluronics poloxamers, and necessitate the warming of the solution for nanomicelle aggregation, utilizing the dehydrated core profiling portion. This dissolution technique is also employed in preparation of PCCMs, with therapeutic polymer dissolved separately, and nanomicelle aggregates impelled by mixing of the two solutions to stabilize therapeutic-polymer ionic proportions [70,71]. The drawback of this technique is the low drug loading that occurs in nanomicelles [60,72].…”

Molecular engineering of polymeric supra-amphiphiles

“…13). 33 The shell of poly(acrylic acid)-block-poly(2-hydroxyethyl acrylate) was bound to the core of a polystyrene-graft-poly(2-vinylpyridine) copolymer. In water, they were dispersed as polyioncomplex (PIC) micelles whose diameter ranged from 42 to 67 nm.…”

“…The star-type polymeric supra-amphiphile that was dispersed as polyion complex (PIC) micelles. Reprinted from ref 33. with permission from the American Chemical Society.…”