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

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 (90–150 nm) 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.