Multi-armed poly(aspartate-g-OEI) copolymers as versatile carriers of pDNA/siRNA

Abstract

To search for potential non-viral nucleic acids carriers, a series of novel cationic polymers, multi-armed poly(aspartate-graft-oligoethylenimine) (MP-g-OEI) copolymers were designed and synthesized by grafting different types of oligoethylenimine (OEI) to a multi-armed poly(l-aspartic acid) backbone. The as-synthesized MP-g-OEI copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance and gel permeation chromatography. These MP-g-OEI copolymers (MP423, MP600 and MP1800) exhibited good capacity in condensing nucleic acids (pDNA or siRNA) into nanosized particles (90–150nm) with positive surface charges. Gene transfection activity of the MP-g-OEI copolymers (especially MP1800) showed improved performance compared with PEI25k in both HeLa and CHO cell lines. The silencing efficiency of MP600/siRNA and MP1800/siRNA complexes showed a superior knockdown effect in CT26 and Huh-7 cell lines. Moreover, the MP-g-OEI copolymers exhibited much lower cytotoxicity than PEI25k. Flow cytometric analysis showed that MP-g-OEI copolymers could efficiently mediate the entry of nucleic acids into cells. These results suggest that MP-g-OEI copolymers may be potential non-viral gene carriers for the delivery of nucleic acids in future gene therapy.