Seyed Mohammad Motevalli, Ahmed Shaker Eltahan, Lu Liu, Andrea Magrini, Nicola Rosato, Weisheng Guo, Massimo Bottini, Xing-Jie Liang. Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells. Biophysics Reports, 2019, 5(1): 19-30. doi: 10.1007/s41048-018-0079-6
Citation: Seyed Mohammad Motevalli, Ahmed Shaker Eltahan, Lu Liu, Andrea Magrini, Nicola Rosato, Weisheng Guo, Massimo Bottini, Xing-Jie Liang. Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells. Biophysics Reports, 2019, 5(1): 19-30. doi: 10.1007/s41048-018-0079-6

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

doi: 10.1007/s41048-018-0079-6
Funds:  The authors gratefully acknowledge that this work was financially supported by the National Natural Science Foundation of China (31430031, 51373117, and 51573128) and National Distinguished Young Scholars grant (31225009). The authors also appreciate the support by the external cooperation program of BIC, Chinese Academy of Science (121D11KYSB20130006), the“Strategic Priority Research Program”of the Chinese Academy of Sciences (XDA09030301), and the NanOArt grant of the“Mission Sustainability”of the University of Rome Tor Vergata.
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  • Corresponding author: Massimo Bottini, Xing-Jie Liang
  • Received Date: 17 May 2018
  • Rev Recd Date: 27 August 2018
  • Publish Date: 28 February 2019
  • 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 with 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.
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