载金阿霉素纳米偶联物克服多药耐药性。

Gold-doxorubicin nanoconjugates for overcoming multidrug resistance.

机构信息

Department of Biology and Chemistry, The City University of Hong Kong, Kowloon, Hong Kong, China.

出版信息

Nanomedicine. 2012 Feb;8(2):204-11. doi: 10.1016/j.nano.2011.06.005. Epub 2011 Jun 24.

DOI:10.1016/j.nano.2011.06.005

PMID:21704592

Abstract

UNLABELLED

Multidrug resistance (MDR) is a major clinical obstacle to the success of cancer chemotherapy. Here we developed a gold-doxorubicin (DOX) nanoconjugates system to overcome MDR. Gold nanoparticles (AuNPs) were first PEGylated as Au-PEG-NH(2), and DOX was then grafted onto AuNPs via a cleavable disulfide linkage (Au-PEG-SS-DOX). Confocal images revealed that the extent of intracellular uptake of Au-PEG-SS-DOX was greater than that of free DOX in the MDR cells, and inductively coupled plasma mass spectroscopy analysis further confirmed that AuNPs significantly increased the level of drug accumulation in MDR cells at a nanoparticles dose greater than 15 μM. The cytotoxicity study demonstrated that the Au-PEG-SS-DOX nanoconjugates system efficiently released the anticancer drug DOX and enhanced its cytotoxicity against MDR cancer cells. This study highlights the potential of using AuNPs for overcoming of MDR in cancer chemotherapy.

FROM THE CLINICAL EDITOR

This study demonstrates that gold nanoparticles can be successfully applied to overcome MDR in cancer chemotherapy.

摘要

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多药耐药（MDR）是癌症化疗成功的主要临床障碍。在这里，我们开发了一种金-阿霉素（DOX）纳米缀合物系统来克服 MDR。首先将金纳米粒子（AuNPs）聚乙二醇化得到 Au-PEG-NH（2），然后通过可裂解的二硫键（Au-PEG-SS-DOX）将 DOX 接枝到 AuNPs 上。共焦图像显示，在 MDR 细胞中，Au-PEG-SS-DOX 的细胞内摄取程度大于游离 DOX，电感耦合等离子体质谱分析进一步证实，在纳米粒子剂量大于 15 μM 时，AuNPs 显著增加了药物在 MDR 细胞中的积累水平。细胞毒性研究表明，Au-PEG-SS-DOX 纳米缀合物系统能有效释放抗癌药物 DOX，并增强其对 MDR 癌细胞的细胞毒性。这项研究强调了使用 AuNPs 克服癌症化疗中 MDR 的潜力。