Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan, 430072, People's Republic of China.
Nanotechnology. 2017 Feb 24;28(8):085603. doi: 10.1088/1361-6528/aa5715. Epub 2017 Jan 5.
Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.
在此,我们制备了叶酸靶向的核交联聚合物胶束(CCL/FA),其中包含多个位于胶束界面和核中的二硫键,用于共递送多柔比星(DOX)和 P 糖蛋白(P-gp)抑制剂他利喹达(TQR)以逆转耐药性。通过形态、分子量和水动力粒径的变化,评估了 CCL/FA 胶束的稳定性和氧化还原响应行为。一方面,胶束具有良好的稳定性,这导致在生理环境中抑制了 CCL 胶束中药物的释放。另一方面,在还原条件下,CCL 胶束迅速崩溃并显著加速药物释放。体外细胞毒性测量,结合共聚焦激光扫描显微镜(CLSM)和流式细胞术,证实了载双药的胶束对 MCF-7/ADR 耐药细胞的细胞毒性明显高于游离多柔比星盐酸盐、单载药 CCL 胶束和非靶向 CCL 胶束。结果表明,通过 CCL/FA 胶束共递送 DOX 和 TQR 可能是克服肿瘤治疗中多药耐药的一种有前途的方法。
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