Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Macromol Biosci. 2018 Jan;18(1). doi: 10.1002/mabi.201700194. Epub 2017 Aug 4.
Chloroquine-containing 2-(dimethylamino)ethyl methacrylate copolymers (PDCs) are synthesized by reversible addition-fragmentation chain-transfer polymerization. Systematic evaluation is 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 PDC/miRNA polyplexes through inhibition of cancer cell migration. The results show that miRNA delivery efficiency is dependent both on the molecular weight and CQ. The best performing PDC/miRNA polyplexes show effective endosomal escape of miRNA. PDC polyplexes with therapeutic miR-210 show promising anticancer activity in human breast cancer cells. PDC/miRNA polyplexes show 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 anti-metastatic and anticancer miRNA therapeutic strategies.
含氯喹的 2-（二甲氨基）乙基甲基丙烯酸酯共聚物（PDCs）通过可逆加成-断裂链转移聚合合成。系统评估是为了检验以下假设：PDC 结构中存在氯喹（CQ）将通过增强内涵体逃逸来提高 miRNA 的递送效率，同时通过抑制癌细胞迁移来提高 PDC/miRNA 复合物的抗癌活性。结果表明，miRNA 的递送效率既依赖于分子量又依赖于 CQ。表现最好的 PDC/miRNA 复合物显示出有效的 miRNA 内涵体逃逸。具有治疗性 miR-210 的 PDC 复合物在人乳腺癌细胞中表现出有前途的抗癌活性。PDC/miRNA 复合物具有抑制癌细胞迁移的优异能力。总的来说，这项研究支持使用 PDC 作为一种有前途的聚合物药物平台，用于联合抗转移和抗癌 miRNA 治疗策略。
