Synthesis and Evaluation of Chloroquine-Containing DMAEMA Copolymers as Efficient Anti-miRNA Delivery Vectors with Improved Endosomal Escape and Antimigratory Activity in Cancer Cells.

Synthesis and Evaluation of Chloroquine-Containing DMAEMA Copolymers as Efficient Anti-miRNA Delivery Vectors with Improved Endosomal Escape and Antimigratory Activity in Cancer Cells.
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DOI:
10.1002/mabi.201700194
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发表时间:
2018-01
影响因子:
4.6
通讯作者:
Oupický D
Oupický D
中科院分区:
工程技术3区
文献类型:
--
作者:
Xie Y;Yu F;Tang W;Alade BO;Peng ZH;Wang Y;Li J;Oupický D

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通过可逆加成断裂链转移(RAFT)聚合合成了含氯喹的甲基丙烯酸2-(二甲氨基)乙酯(DMAEMA)共聚物(PDC)。进行系统评估以检验以下假设:PDC 结构中氯喹 (CQ) 的存在将由于增强的内体逃逸而改善 miRNA 的递送,同时通过抑制癌细胞迁移而有助于 PCD/miRNA 复合物的抗癌活性。我们的结果表明 miRNA 递送效率取决于分子量和 CQ。性能最好的 PDC/miRNA 复合物显示出 miRNA 的有效内体逃逸。具有治疗性 miR-210 的 PDC 复合物在人类乳腺癌细胞中显示出有希望的抗癌活性。 PDC/miRNA复合物表现出优异的抑制癌细胞迁移的能力。总体而言,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。
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.
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