A nuclear targeted Dox-aptamer loaded liposome delivery platform for the circumvention of drug resistance in breast cancer
A nuclear targeted Dox-aptamer loaded liposome delivery platform for the circumvention of drug resistance in breast cancer
复制标题
用于规避乳腺癌耐药性的核靶向 Dox 适体负载脂质体递送平台
DOI：
10.1016/j.biopha.2019.109072
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发表时间：
2019-09-01
影响因子：
7.5
通讯作者：
Rao, Yuefeng
中科院分区：
文献类型：
--
作者：
Li, Xin;Wu, Xiuhua;Rao, Yuefeng
肿瘤多药耐药（multidrug resistance，MDR）已成为肿瘤治疗中日益严重的问题。P-糖蛋白（P-gp）在细胞膜上的过度表达是多药耐药的主要机制之一。核靶向纳米药物递送系统，使抗癌药物的核内释放，有望解决这一挑战。本研究利用核仁素主动转运至细胞核的特性及其与核酸适体的亲和性，开发了一种核靶向给药系统（MCF-7/Adr），以规避乳腺癌耐药。将插入适体AS 1411（Ap-Dox）中的Dox中心点HCl包封在脂质体（Lip（Ap-Dox））的水性内部中。体外研究表明，Lip-Dox复合物扩散进入MCF-7/Adr细胞后，与核仁素发生强烈结合，最终进入细胞核。通过使用这种药物递送系统，Dox中心点HCl可以有效地积聚在细胞核中，从而有效地杀死癌细胞。
The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs in the cytoplasm from the cell, is a major mechanism of MDR. Nuclear-targeted nanoparticle drug delivery system, which enables intranuclear release of anticancer drugs, is expected to address this challenge. In this study, based on nucleolin's active transport property to the nucleus and its affinity with aptamer, we developed a nuclear-targeted delivery system to circumvention of drug resistance in breast cancer (MCF-7/Adr). Dox center dot HCl inserted in the aptamer AS1411 (Ap-Dox) was encapsulated in the aqueous interior of liposome (Lip(Ap-Dox)). In vitro studies showed that after the Lip(Ap-Dox) diffusing into MCF-7/Adr cells, Ap-Dox complex bound with nucleolin strongly and eventually entered the cell nuclei. By using this drug delivery system, Dox center dot HCl can efficiently accumulated in the nuclei to effectively kill the cancer cells.