Controlled Intracellular Polymerization for Cancer Treatment

Yichuan Zhang; Quan Gao; Weishuo Li; Rongkun He; Liwei Zhu; Qianjin Lian; Liang Wang; Yang Li; Mark Bradley; Jin Geng

doi:10.1021/jacsau.1c00373

Controlled Intracellular Polymerization for Cancer Treatment

JACS Au. 2022 Feb 23;2(3):579-589. doi: 10.1021/jacsau.1c00373. eCollection 2022 Mar 28.

Authors

Yichuan Zhang¹, Quan Gao¹, Weishuo Li², Rongkun He¹, Liwei Zhu¹, Qianjin Lian¹, Liang Wang¹, Yang Li¹, Mark Bradley³, Jin Geng¹

Affiliations

¹ Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518059, China.
² Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
³ EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, U.K.

Abstract

Numerous prodrugs have been developed and used for cancer treatments to reduce side effects and promote efficacy. In this work, we have developed a new photoactivatable prodrug system based on intracellular photoinduced electron transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization. This unique polymerization process provided a platform for the synthesis of structure-predictable polymers with well-defined structures in living cells. The intracellularly generated poly(N,N-dimethylacrylamide)s were found to induce cell cycle arrest, apoptosis, and necroptosis, inhibit cell proliferation, and reduce cancer cell motilities. This polymerization-based "prodrug" system efficiently inhibits tumor growth and metastasis both in vitro and in vivo and will promote the development of targeted and directed cancer chemotherapy.