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通过共递送阿霉素和姜黄素聚合物胶束协同提高抗肿瘤疗效

Synergistically Improved Anti-tumor Efficacy by Co-delivery Doxorubicin and Curcumin Polymeric Micelles.

作者信息

Wang Jinling, Ma Wenzhuan, Tu Pengfei

机构信息

Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, PR China.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, PR of China.

出版信息

Macromol Biosci. 2015 Sep;15(9):1252-61. doi: 10.1002/mabi.201500043. Epub 2015 May 15.

Abstract

P-gp mediated drug efflux has been recognized as a major obstacle limiting the success of cancer chemotherapy. To overcome this issue, doxorubicin (DOX) and curcumin (Cur; P-gp inhibitor and apoptosis inhibitor) co-encapsulated pegylated polymeric micelles ((DOX+Cur)-PMs) were designed, prepared and characterized to simultaneously deliver chemotherapeutic drug and multidrug resistance (MDR) modulator to tumor sites. The (DOX+Cur)-PMs were spherical nano-size particle, with a loading content of 6.83%, and high colloidal stability. Co-delivery micelles exhibited excellent cytotoxicity by reversing MDR, promoting cellular uptake and enhancing cellular apoptosis in MCF7/Adr cells. The tumor growth inhibitory effect of (DOX+Cur)-PMs in 4T1-bearing mice was more effective compared with the combination solution of DOX and Cur and even DOX-PMs. In conclusion, simultaneous delivery of DOX and Cur by (DOX+Cur)-PMs has been demonstrated to be a promising approach for overcoming MDR and improving antitumor efficacy.

摘要

P-糖蛋白介导的药物外排已被认为是限制癌症化疗成功的主要障碍。为克服这一问题,设计、制备并表征了阿霉素(DOX)和姜黄素(Cur;P-糖蛋白抑制剂及凋亡抑制剂)共包封的聚乙二醇化聚合物胶束((DOX+Cur)-PMs),以便将化疗药物和多药耐药(MDR)调节剂同时递送至肿瘤部位。(DOX+Cur)-PMs为球形纳米尺寸颗粒,载药量为6.83%,且具有高胶体稳定性。共递送胶束通过逆转多药耐药、促进细胞摄取及增强MCF7/Adr细胞的细胞凋亡而表现出优异的细胞毒性。与DOX和Cur的联合溶液甚至DOX-PMs相比,(DOX+Cur)-PMs对荷4T1小鼠的肿瘤生长抑制作用更有效。总之,(DOX+Cur)-PMs同时递送DOX和Cur已被证明是一种克服多药耐药及提高抗肿瘤疗效的有前景的方法。

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