近日,，中科院上海藥物研究所李亞平課題組與上海硅酸鹽研究所施建林研究員課題組合作,，在通過納米載體調控細胞內藥物釋放降低腫瘤耐藥研究中取得重要進展,。相關研究結果發(fā)表在納米技術領域期刊Acs Nano,。
多藥耐藥現(xiàn)象是癌癥治療的主要障礙之一,，而化療藥物的納米輸送系統(tǒng)有望提高對耐藥腫瘤的治療效果,。上海硅酸鹽所施建林課題組長期致力于介孔二氧化硅納米粒(MSNs)的制備和應用基礎研究,，而上海藥物所李亞平研究組在納米技術降低腫瘤耐藥性方面有豐富積累,。近年來，兩課題組開展合作,，以MSNs為可控型的納米載體,，探索了納米載體調控細胞內藥物釋放降低腫瘤耐藥性。雙方設計并制備了不同釋藥孔徑的中空二氧化硅納米粒(HMSNs),，作為抗癌藥物阿霉素(DOX)的載體,，通過控制MSNs的釋藥孔徑，調節(jié)藥物的細胞攝取,，通過MSNs的釋藥孔徑差異,，調控DOX的釋放速率，抑制P-gp和消耗ATP等途徑,，克服腫瘤多藥耐藥,。
為調控DOX的胞內釋放速率，上海硅酸鹽所博士研究生陳雨等制備了粒徑200nm,，孔徑分別為3.2nm,、6.4nm和12.8nm的三種HMSNs，上海藥物所高瑜等開展了HMSNs在腫瘤多藥耐藥細胞中的生物學評價,。作為一種新型孔徑可控的無機納米載體,，HMSNs在MCF-7細胞和耐藥的MCF-7/ADR細胞中均能有效被攝取，且細胞毒性低,，HMSNs不僅有較強的載DOX能力和pH-響應性釋藥性質,，而且其細胞外和細胞內藥物釋放均顯示孔徑依賴性的藥物釋放行為,。
另外，載DOX的HMSNs (DMSNs)在MCF-7/ADR細胞中的抗癌活性也呈孔徑依賴性,，較大孔徑的DMSNs能介導更多DOX的細胞攝取和更快的胞內藥物釋放,，在胞內藥物蓄積量更高，逆轉耐藥效果更佳,。該研究對通過納米技術降低腫瘤多藥耐藥的機理研究具有重要參考價值,。（生物谷Bioon.com）
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doi:10.1021/nn2033105
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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.
