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Biophysics Reports 2019, 5(1): 19-30 https://doi.org/10.1007/s41048-018-0079-6
Research Article | Open Access | Issue | Published: 11 January 2019

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

Show Author's Information Seyed Mohammad Motevalli1,2,  Ahmed Shaker Eltahan1,2,  Lu Liu1,2,3,  Andrea Magrini4,5,  Nicola Rosato3,5,  Weisheng Guo1,  Massimo Bottini1,3,5,6( ),  Xing-Jie Liang1,2( )
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Nanoscience & Nanotechnology & Innovative Instrumentation (NAST) Centre, University of Rome Tor Vergata, 00133 Rome, Italy
Inflammatory and Infectious Disease Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Keywords:
Curcumin, Doxorubicin, Albumin nanoparticles, P-glycoprotein, Lysosomal pH
Cite this article:
Motevalli SM, Eltahan AS, Liu L, et al. Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells. Biophysics Reports, 2019, 5(1): 19-30. https://doi.org/10.1007/s41048-018-0079-6
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Abstract Full text About this article

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 ATT and 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 intra-cellular 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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About this article

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

Show Author's information Seyed Mohammad Motevalli1,2, Ahmed Shaker Eltahan1,2, Lu Liu1,2,3, Andrea Magrini4,5, Nicola Rosato3,5, Weisheng Guo1, Massimo Bottini1,3,5,6( ), Xing-Jie Liang1,2( )
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Nanoscience & Nanotechnology & Innovative Instrumentation (NAST) Centre, University of Rome Tor Vergata, 00133 Rome, Italy
Inflammatory and Infectious Disease Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA

Abstract

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 ATT and 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 intra-cellular 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.

Keywords: Curcumin, Doxorubicin, Albumin nanoparticles, P-glycoprotein, Lysosomal pH

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Publication history

Received: 17 May 2018
Accepted: 27 August 2018
Published: 11 January 2019
Issue date: February 2019

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© The Author(s) 2019

Acknowledgements

Acknowledgements

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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