Synthesis of zwitterionic chimeric polymersomes for efficient protein loading and intracellular delivery

Abstract

A novel zwitterionic triblock copolymer of poly(dimethylamino carbonate)-polycaprolactone-poly((2-(methacryloyloxy)ethyl)dimethyl-(3-sulfopropyl)ammonium) [PAC(DMA)-PCL-PMDMSA] was designed and synthesized via sequential ring-opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization successively. The ¹H NMR and GPC results showed that the copolymers were synthesized in a well-defined structure and with a controlled molecular weight. The final triblock copolymer could be self-assembled into zwitterionic chimeric polymersomes (ZPS) consisting of a cation-rich PAC(DMA) inner shell and a zwitterionic hydrophilic PMDMSA shell. TEM, DLS, fluorescence microscopy, flow cytometry and in vitro cell experiments were applied to confirm that the ZPS possessed a defined polymersome structure, excellent stability with high protein loading, good biocompatibility and cell transmembrane ability. Furthermore, cytochrome c-loaded ZPS exhibited potent cancer inhibitory activity and apoptosis-inducing ability against HeLa cells. Overall, the biodegradable ZPS provide an effective platform for the intracellular delivery of therapeutic proteins.