Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

查看全文 作　　者：Seyed Mohammad [1,2]Motevalli;Ahmed Shaker [1,2]Eltahan;Lu [1,2,3]Liu;Andrea [4,5]Magrini;Nicola [3,5]Rosato;Weisheng [1]Guo;Massimo [1,3,5,6]Bottini;Xing-Jie [1,2]Liang

机构地区：[1]CAS Key Laboratory for Biomedical Effects of Nano materials and Nanosafety,CAS Center for Excellence in Nanoscience,National Center for Nano science and Tech nology of China,Beiji ng 100190,China;[2]University of Chinese Academy of Sciences,Beijing 100049,China;[3]Department of Experimental Medicine,University of Rome Tor Vergata,Via Montpellier 1,00133 Rome,Italy;[4]Department of Biomedicine and Prevention,University of Rome Tor Vergata,Via Montpellier 1,00133 Rome,Italy;[5]Nanoscience & Nanotechnology & Irmovative Instrumentation (NAST) Centre,University of Rome Tor Vergata,00133 Rome,Italy;[6]Inflammatory and Infectious Disease Center,Sanford-Burnham Medical Research Institute,10901 North Torrey Pines Road,La Jolla,CA 92037,USA

出　　处：《Biophysics Reports》索引2019年第5卷第1期,共12页

基　　金：the National Natural Science Foundation of China (31430031, 51373117, and 51573128];National Distinguished Young Scholars grant (31225009);the external cooperation program of BIC, Chinese Academy of Science (121 DI 1KYSB20130006);the 'Strategic Priority Research Program of the Chinese Academy of Sciences (XDA09030301);the NanOArt grant of the 'Mission Sustainability' of the University of Rome Tor Vergata. 摘　　要：The adaptive treatment tolerance (ATT) of cancer cells is the main encumbrance to cancer chemotherapy. A potential solution to this problem is to treat cancer cells with multiple drugs using nanoparticles (NPs). In this study, we tested the co-administration of curcumin (Cur) and doxorubicin (Dox) to MCF-7 resistant breast cancer cells to block the ATTand elicit efficient cell killing. Drugs were co-administered to cells both sequentially and simultaneously. Sequential drug co-administration was carried out by pre-treating the cells with albumin nanoparticles (ANPs) loaded w让h Cur (Cur@ANPs) followed by treatment with Dox-loaded ANPs (Dox@ANPs). Simultaneous drug co-administration was carried out by treating the cells with ANPs loaded with both the drugs (Cur/Dox@ANPs). We found that the simultaneous drug co-administration led to a greater intra-cellular accumulation of Dox and cell killing with respect to the sequential drug co-administration. However;the simultaneous drug co-administration led to a lower intracellular accumulation of Cur with respect to the sequential drug co-administration. We showed that this result was due to the aggregation and entrapment of Cur in the lysosomes as soon as it was released from Cur@ANPs, a phenomenon called lysosomotropism. In contrast, the simultaneous release of Dox and Cur from Cur/Dox@ANPs into the lysosomes led to lysosomal pH elevation, which, in turn, avoided Cur aggregation, led to lysosome swelling and drug release in the cytosol, and finally provoked efficient cell killing. Our study shed the light on the molecular processes driving the therapeutic effects of anti-cancer drugs co-administered to cancer cells in different manners. 关键词：ALBUMIN nanoparticles DOXORUBICIN CURCUMIN P-GLYCOPROTEIN LYSOSOMAL pH

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Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

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