Biodegradable mPEG-b-P(MCC-g-OEI) copolymers for efficient gene delivery

Abstract

Cationic polymers play an important role in gene delivery. To search for potential non-viral gene carriers, a series of biodegradable cationic polymers, poly(ethylene glycol)-block-poly(carbonates-graft-oligoethylenimine) [mPEG-b-P(MCC-g-OEI), PPO] copolymers, were synthesized by grafting different kinds of oligoethylenimine (OEI) to the same biodegradable backbone, a derivative of poly(ethylene glycol)-block-polycarbonates. The as-synthesized PPO copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and gel permeation chromatography. Two of the as-synthesized PPO copolymers (PPO600 and PPO1800) could efficiently condense DNA into nanosized particles (100-140 nm) with positive surface charges when the PPO/DNA mass ratio is above 10:1. The cell toxicity and gene transfection evaluations show that PPO copolymers, especially PPO1800, which exhibits lower cytotoxicity and higher gene transfection efficiency than PEI25K in the absence and the presence of serum in the CHO and COS-7 cell lines, have great potential as non-viral gene carriers. The PPO1800 copolymer images obtained by confocal laser scanning microscopy prove that PPO copolymers could efficiently mediate the entry of plasmid DNA into cells. These results show that PPO copolymers may be potential non-viral gene carriers in future applications of gene therapy.