Synthesis and biological characterization of clicked chloroquine copolymers as macromolecular inhibitors of cancer cell migration

We report synthesis of nondegradable chloroquine (CQ)-containing N-(2-hydroxyethyl)methacrylamide (HPMA) copolymers (pCQ2) by a combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and click chemistry. The ability of the copolymers to inhibit cancer cell migration was compared to our previously reported degradable pCQ1 in breast cancer cells utilizing transwell and wound healing assays. Both cleavable and noncleavable pCQ demonstrated enhanced inhibitory activity when compared with small-molecule CQ. This study validates that pCQ2 functions as a macromolecular inhibitor of cancer cell migration without the need for CQ release and provides support for pCQ as a new class of antimetastatic polymer agents with a possibly unique mechanism of action. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2235-2242