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

Bingbing Zhao; Yuting Yan; Junmei Zhang; Enping Chen; Ke Wang; Changshun Zhao; Yinan Zhong; Dechun Huang; Zhiqin Cui; Dawei Deng; Congying Gu; Wei Chen

doi:10.1039/D1PY00815C

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

Bingbing Zhao,^a Yuting Yan,^a Junmei Zhang,^a Enping Chen,^a Ke Wang,^a Changshun Zhao,^a Yinan Zhong,^a Dechun Huang,^a Zhiqin Cui,*^a Dawei Deng,

^b Congying Gu*^c and Wei Chen

*^a

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* Corresponding authors

^a Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China
E-mail: zhiqin.cui@163.com, w.chen@cpu.edu.cn

^b Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China

^c School of Science, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China
E-mail: 1020031086@cpu.edu.cn

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.

Polymer Chemistry

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

Abstract

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

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