Chloroquine-containing DMAEMA copolymers as efficient anti-miRNA delivery vectors with improved endosomal escape and anti-migratory activity in cancer cells

摘要

Chloroquine-containing 2-(dimethylamino)ethyl methacrylate (DMAEMA) copolymers (PDCs) were synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Systematic evaluation was performed to test the hypothesis that presence of chloroquine (CQ) in the PDC structure will improve miRNA delivery due to enhanced endosomal escape while simultaneously contribute to anticancer activity of PCD/miRNA polyplexes through inhibition of cancer cell migration. Our results showed that miRNA delivery efficiency was dependent both on the molecular weight and CQ. The best performing PDC/miRNA polyplexes showed effective endosomal escape of miRNA. PDC polyplexes with therapeutic miR-210 showed promising anticancer activity in human breast cancer cells. PDC/miRNA polyplexes showed excellent ability to inhibit migration of cancer cells. Overall, this study supports the use of PDC as a promising polymeric drug platform for use in combination antimetastatic and anticancer miRNA therapeutic strategies.