Novel poly(glycidyl methacrylate-b-propylene oxide-b-glycidyl methacrylate) derivatives with low cytotoxicity and efficient gene delivery

Abstract

Gene therapy has been developed for decades, but is still hampered for general clinical treatment by lack of gene delivery vectors with high transfection efficiency and low cytotoxicity. In this study, well-defined BAB triblock copolymer, poly(glycidyl methacrylate-b-propylene oxide-b-glycidyl methacrylate), P(GMA-b-PO-b-GMA), was prepared via atom transfer radical polymerization and modified by different ratios of ethylenediamine (EDA) and 1-(3-aminopropyl) imidazole (API) to obtain cationic amphiphilic polymers. The difference in the ratio of EDA and API had an influence on pDNA-binding capability, size, and zeta potential of P(GMA-b-PO-b-GMA) derivatives. All the cationic amphiphilic polymers exhibited low cytotoxicity and good transfection activity in comparison with 25 kDa polyethylenimine (PEI) due to their special architecture. The optimal polymer, with 89% API and 11% EDA, showed the highest transfection efficiency among these polymers. Its luciferase expression at N/P ratio of 30 was comparable to that of 25 kDa PEI in a serum-free medium and higher than that of 25 kDa PEI by roughly an order of magnitude in a medium with serum.