Overcoming tumor resistance to cisplatin through micelle-mediated combination chemotherapy
Overcoming tumor resistance to cisplatin through micelle-mediated combination chemotherapy
复制标题
通过胶束介导的联合化疗克服肿瘤对顺铂的耐药性
DOI：
10.1039/c4bm00305e
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发表时间：
2015
影响因子：
6.6
通讯作者：
Huang Yubin
中科院分区：
文献类型：
--
作者：
Zhou Dongfang;Cong Yuwei;Qi Yanxin;He Shasha;Xiong Hejian;Wu Yanjuan;Xie Zhigang;Chen Xuesi;Jing Xiabin;Huang Yubin
The main obstacles to cancer therapy are the inability to target cancer cells and the acquired drug resistance after a period of chemotherapy. Reduced drug uptake and DNA repair are the two main mechanisms involved in cisplatin resistance. In the present investigation, canthaplatin, a Pt(IV) pro-drug of cisplatin and a protein phosphatase 2A (PP2A) inhibitor (4-(3-carboxy-7-oxa-bicyclo[2.2.1]heptane-2-carbonyl)piperazine-1-carboxylic acid tert-butyl ester), was designed and delivered using PEG-b-PLGA micelles for combination chemotherapy. Polymer/canthaplatin micelles facilitated the delivery of the drug into cancer cells through endocytosis and diminished DNA repair by PP2A inhibition, resulting in enhanced anti-tumor efficiency and excellent reversal ability of tumor resistance to cisplatin both in vitro and in vivo. Additionally, the polymer/canthaplatin micelles could prolong drug residence in the blood and decrease the side effects when compared to cisplatin.
