Bioreducible Micelles with Endosomal Buffering and Multidrug Resistance-Reversing Function Enhance Anti-Tumor Efficacy of Doxorubicin.
Bioreducible Micelles with Endosomal Buffering and Multidrug Resistance-Reversing Function Enhance Anti-Tumor Efficacy of Doxorubicin.
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DOI：
10.1166/jbn.2015.2004
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发表时间：
2015-10
影响因子：
2.9
通讯作者：
Qi Yin;Jianan Shen;Haijun Yu;Yongzhuo Huang;Zhiwen Zhang;Yaping Li
中科院分区：
文献类型：
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作者：
Qi Yin;Jianan Shen;Haijun Yu;Yongzhuo Huang;Zhiwen Zhang;Yaping Li
蒽环类药物治疗乳腺癌的临床成功主要受到心脏损害和多药耐药（MDR）的限制。为有效逆转阿霉素（DOX）的耐药性，以聚乙二醇（PEG）和聚[双（2-羟乙基）-二硫代-二丙烯酸酯-β-组胺]（poly[bis（2-hydroxyethyl）-disulfide-diacrylate-β-histamine]）为原料，制备了DOX多功能生物可还原胶束。咪唑基团的引入使胶束具有缓冲内体的能力，并促进了内体逃逸。胶束的还原响应性促进了DOX的释放。P-糖蛋白，一个最好描述的药物外排泵，和谷胱甘肽S-转移酶，一个重要的解毒酶的活性，也被胶束抑制。静脉注射载药胶束后，耐药荷瘤小鼠肿瘤中DOX的蓄积增加。这些结果表明，胶束是一种很有前途的多药耐药肿瘤治疗药物传递系统。
The clinical success of anthracyclines-containing chemotherapy for breast cancer is mainly restricted by cardiac damage and the development of multidrug resistance (MDR). For efficient reversal of drug resistance, doxorubicin (DOX) loaded multifunctional bioreducible micelles were constructed from a new amphiphilic copolymer consisting of polyethylene glycol and poly[bis(2-hydroxylethyl)-disulfide-diacrylate-β-histamine and characterized. The introduction of imidazole group endowed the micelles with endosomal buffering capacity and improved the endosomal escape. The reduction-responsiveness of the micelles promoted DOX release. The activity of P-glycoprotein, one of the most well-described drug-efflux pumps, and glutathione S-transferase, an important detoxification enzyme, were also inhibited by the micelles. The accumulation of DOX in tumor after intravenous administration of the drug-loading micelles was increased in drug resistant tumor-bearing mice. These results indicated that the micelle was a promising drug delivery system for MDR cancer therapy.