A novel kind of pH-sensitive brush copolymer [poly(2-hydroxyethyl methacrylate)-graft-poly(ethylethylene phosphate)]-block-poly[2-(dimethylamino)ethyl methacrylate] [(PHEMA-g-PEEP)-b-PDMAEMA] with biodegradable polyphosphoester as the side chains, and its self-assembled aggregates were developed for nonviral gene delivery. The brush copolymers were synthesized via a combination of single-electron transfer living radical polymerization and ring-opening polymerization. The chemical structures of these brush copolymers were characterized by FTIR, 1H NMR, and 31P NMR measurements. The critical aggregation concentration values of (PHEMA-g-PEEP)-b-PDMAEMA in pH 7.4 buffer solution were determined by the fluorescence probe technique. The interaction of (PHEMA-g-PEEP)-b-PDMAEMA and DNA was studied by agarose gel retardation assay, and the formed complexes were further investigated by means of zeta potential, dynamic light scattering, and transmission electron microscopy measurements. In addition, the in vitro cytotoxicity and transfection tests indicated that these brush copolymers showed low toxicity and favorable transfection efficiency to HeLa cells. All these results demonstrated that these biocompatible brush copolymers may be a promising candidate as nonviral polymeric gene vector. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
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