Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles
Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles
复制标题
通过还原敏感的线性阳离子点击聚合物/iMDR1-pDNA复合纳米粒子逆转多药耐药性
DOI：
10.1016/j.biomaterials.2010.11.001
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发表时间：
2011-02-01
期刊：
影响因子：
14
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Gao, Yu;Chen, Lingli;Li, Yaping
A reduction-sensitive linear cationic click polymer (RCP) was specially designed for the efficient gene delivery to overcome multidrug resistance (MDR) by RNA interference to silence the expression of P-glycoprotein (P-gp). RCP was synthesized via the "click chemistry" with disulfide bonds, amide triazole moieties and secondary amine groups in the main chain. RCP could efficiently condense pDNA into nanoparticles (RCPNs) around 150 nm. Polyplex dissociation was observed in the presence of 2.5 mm DTT due to the cleavage of disulfide bonds, which indicated the efficient DNA release under the reduction condition. In vitro transfection and cytotoxicity experiments against human breast cancer MCF-7 cells and drug-resistant MCF-7/ADR cells showed that RCPNs could bring about higher transfection efficiency with much lower cytotoxicity than PEI/DNA nanoparticles. RCPNs loaded with plasmid iMDR1-pDNA could inhibit P-gp expression, increase adriamycin (ADR) accumulation and enhance cytotoxicity of ADR against MCF-7/ADR cells. Combination of RCPNs and ADR could suppress the tumor growth more efficiently than using ADR only on mouse xenograft model bearing ADR resistant human breast cancer. These results suggested that this RCP could be a potential, safe and efficient non-viral vector for reversing MDR. (C) 2010 Elsevier Ltd. All rights reserved.
