Controlled Intracellular Polymerization for Cancer Treatment

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(<i>N</i>,<i>N</i>-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 <i>in vitro</i> and <i>in vivo</i> and will promote the development of targeted and directed cancer chemotherapy.