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通过水凝胶纳米颗粒共递送阿霉素和维拉帕米克服癌症多药耐药性

Overcoming cancer multidrug resistance by codelivery of doxorubicin and verapamil with hydrogel nanoparticles.

作者信息

Qin Ming, Lee Yong-Eun Koo, Ray Aniruddha, Kopelman Raoul

机构信息

Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.

出版信息

Macromol Biosci. 2014 Aug;14(8):1106-15. doi: 10.1002/mabi.201400035. Epub 2014 Apr 28.

Abstract

The efficacy of chemotherapy is often inhibited by multidrug resistance (MDR). A highly engineerable hydrogel nanoparticle (NP) serves as a carrier for the optimal codelivery to tumor cells of the chemodrug, doxorubicin (Dox) and the chemosensitizer, verapamil (Vera), aiming at alleviating tumor MDR. The hydrogel NPs are prepared via the copolymerization of acrylamide and 2-carboxyethyl acrylate. Dox and Vera are post-loaded into the respective NPs, with drug loading around 7.7 wt% and 8.0 wt%, respectively. The codelivery of Dox-NPs and Vera-NPs increases the intracellular accumulation of Dox, and significantly enhances the cell killing ability of Dox with respect to NCI/ADR-RES cells in vitro. These findings suggest that such codelivery nanoplatforms provide a promising route for overcoming tumor MDR.

摘要

化疗的疗效常常受到多药耐药性(MDR)的抑制。一种具有高度可工程化的水凝胶纳米颗粒(NP)作为载体,用于将化疗药物阿霉素(Dox)和化学增敏剂维拉帕米(Vera)最佳地共递送至肿瘤细胞,旨在减轻肿瘤多药耐药性。水凝胶纳米颗粒通过丙烯酰胺和丙烯酸2-羧乙酯的共聚反应制备。Dox和Vera被后装载到各自的纳米颗粒中,药物装载量分别约为7.7 wt%和8.0 wt%。Dox纳米颗粒和Vera纳米颗粒的共递送增加了Dox在细胞内的积累,并显著增强了Dox在体外对NCI/ADR-RES细胞的杀伤能力。这些发现表明,这种共递送纳米平台为克服肿瘤多药耐药性提供了一条有前景的途径。

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