新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 纳米医学 » Acs Nano:李亚平等纳米载体降低肿瘤耐药研究获进展

Acs Nano:李亚平等纳米载体降低肿瘤耐药研究获进展

来源:上海药物研究所 2011-12-09 13:01

近日,中科院上海药物研究所李亚平课题组与上海硅酸盐研究所施建林研究员课题组合作,在通过纳米载体调控细胞内药物释放降低肿瘤耐药研究中取得重要进展。相关研究结果发表在纳米技术领域期刊Acs Nano

多药耐药现象是癌症治疗的主要障碍之一,而化疗药物的纳米输送系统有望提高对耐药肿瘤的治疗效果。上海硅酸盐所施建林课题组长期致力于介孔二氧化硅纳米粒(MSNs)的制备和应用基础研究,而上海药物所李亚平研究组在纳米技术降低肿瘤耐药性方面有丰富积累。近年来,两课题组开展合作,以MSNs为可控型的纳米载体,探索了纳米载体调控细胞内药物释放降低肿瘤耐药性。双方设计并制备了不同释药孔径的中空二氧化硅纳米粒(HMSNs),作为抗癌药物阿霉素(DOX)的载体,通过控制MSNs的释药孔径,调节药物的细胞摄取,通过MSNs的释药孔径差异,调控DOX的释放速率,抑制P-gp和消耗ATP等途径,克服肿瘤多药耐药。

为调控DOX的胞内释放速率,上海硅酸盐所博士研究生陈雨等制备了粒径200nm,孔径分别为3.2nm、6.4nm和12.8nm的三种HMSNs,上海药物所高瑜等开展了HMSNs在肿瘤多药耐药细胞中的生物学评价。作为一种新型孔径可控的无机纳米载体,HMSNs在MCF-7细胞和耐药的MCF-7/ADR细胞中均能有效被摄取,且细胞毒性低,HMSNs不仅有较强的载DOX能力和pH-响应性释药性质,而且其细胞外和细胞内药物释放均显示孔径依赖性的药物释放行为。

另外,载DOX的HMSNs (DMSNs)在MCF-7/ADR细胞中的抗癌活性也呈孔径依赖性,较大孔径的DMSNs能介导更多DOX的细胞摄取和更快的胞内药物释放,在胞内药物蓄积量更高,逆转耐药效果更佳。该研究对通过纳米技术降低肿瘤多药耐药的机理研究具有重要参考价值。(生物谷Bioon.com)

>>延伸阅读:PNAS:高效低毒纳米颗粒抑制耐药肿瘤细胞生长新成果

>>延伸阅读:肿瘤细胞多药耐药基因及产物p糖蛋白检测方法的研究进展

>>延伸阅读:肿瘤细胞多药耐药机理的研究进展

>>延伸阅读:生物物理所抗肿瘤化疗药物纳米载体研究获重大突破

>>延伸阅读:Nature Nanotechnology:新型RNAi药物纳米载体

Controlled Intracellular Release of Doxorubicin in Multidrug-Resistant Cancer Cells by Tuning the Shell-Pore Sizes of Mesoporous Silica Nanoparticles

Yu Gao, Yu Chen, Xiufeng Ji, Xinyu He, Qi Yin, Zhiwen Zhang, Jianlin Shi, and Yaping Li

In this work, hollow mesoporous silica nanoparticles (HMSNs) with three pore sizes were manufactured to control the drug release rate, and the biological roles of these HMSNs were evaluated in multidrug-resistant (MDR) cancer cells. As novel pore-size-controllable inorganic materials, HMSNs showed negligible cytotoxicity and efficient cellular uptake toward drug-sensitive MCF-7 and drug-resistant MCF-7/ADR cells. Doxorubicin (DOX)-loaded HMSNs (DMSNs) not only demonstrated effective drug loading and a pH-responsive drug release character but also exhibited pore-size-dependent and sustained drug release performance in both in vitro and intracellular drug release experiments. In addition, DMSNs exhibited pore-size-dependent anticancer activity against MCF-7/ADR cells. DMSNs with larger pore size could mediate more cellular uptake of DOX and faster intracellular drug release, which led to more intracellular drug accumulation and stronger MDR-reversal effects. The MDR-overcoming mechanism could be due to the efficient cellular uptake, P-gp inhibition, and ATP depletion. These results demonstrate that HMSNs could be a very promising drug delivery system for pore-size-controllable drug release and cancer MDR reversion.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库