Overcoming ABCG2-mediated multidrug resistance by a mineralized hyaluronan-drug nanocomplex
Overcoming ABCG2-mediated multidrug resistance by a mineralized hyaluronan-drug nanocomplex
复制标题
通过矿化透明质酸药物纳米复合物克服 ABCG2 介导的多药耐药性
DOI：
10.1039/c6tb01545j
复制
发表时间：
2016-01-01
影响因子：
7
通讯作者：
Fu, Liwu
中科院分区：
文献类型：
--
作者：
Chen, Wei;Wang, Fang;Fu, Liwu
由细胞膜ATP结合盒（ABC）转运蛋白过度表达引起的多药耐药（MDR）是肿瘤化疗的主要障碍。在各种转运蛋白中，ATP结合盒亚家族G成员2（ABCG 2）已经获得越来越多的关注，因为它已被证明在各种癌细胞甚至许多癌症干细胞中起关键作用。在这项研究中，我们开发了一种新的多组分纳米复合物，通过使用一个简单的透明质酸为基础的仿生矿化反应，同时封装酪氨酸激酶抑制剂（阿法替尼）作为非传统的ABCG2抑制剂和抗癌药物（阿霉素）作为细胞凋亡诱导剂。所得纳米复合物可通过同步增强药物摄取和抑制药物外排来实现克服ABCG 2介导的MDR的高度协同效应。因此，通过靶向仿生途径实现多组分的时空同步将为ABCG 2介导的耐药癌症的化疗带来巨大希望。
Multidrug resistance (MDR), caused by the overexpression of ATP-binding cassette (ABC) transporters on the cell membrane, is a major obstacle in the chemotherapy of cancers. Among various transporters, ATP-binding cassette subfamily G member 2 (ABCG2) has garnered increasing attention as it has been proven to play a critical role in various cancer cells and even in many cancer stem cells. In this study, we developed a novel multicomponent nanocomplex by using a simple hyaluronan-based biomimetic mineralization reaction to simultaneously encapsulate a tyrosine kinase inhibitor (afatinib) as a non-traditional ABCG2 inhibitor and an anticancer drug (doxorubicin) as an apoptosis inducer. The resulting nanocomplex can achieve a highly synergistic effect to overcome ABCG2-mediated MDR by synchronously enhancing drug uptake and inhibiting drug efflux. It follows that a spatial-temporal synchronization of multiple components via a targeted biomimetic pathway would hold great promise for chemotherapy of ABCG2-mediated resistant cancers.