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Issue 7, 2018
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Synergistic breast tumor cell killing achieved by intracellular co-delivery of doxorubicin and disulfiram via core–shell–corona nanoparticles

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Abstract

Combination therapy with different functional chemotherapeutic agents based on nano-drug delivery systems is an effective strategy for the treatment of breast cancer. However, co-delivery of drug molecules with different physicochemical properties still remains a challenge. In this study, an amphiphilic poly (ε-caprolactone)-b-poly (L-glutamic acid)-g-methoxy poly (ethylene glycol) (PCL-b-PGlu-g-mPEG) copolymer was designed and synthesized to develop a nanocarrier for the co-delivery of hydrophilic doxorubicin (DOX) and hydrophobic disulfiram (DSF). The amphiphilic copolymer self-assembled into core–shell–corona structured nanoparticles with the hydrophobic PCL core for DSF loading (hydrophobic interaction) and anionic poly (glutamic acid) shell for DOX loading (electrostatic interaction). DSF and DOX co-loaded nanoparticles (Co-NPs) resulted in high drug loading and precisely controlled DSF/DOX ratio via formulation optimization. Compared with free drug solutions, DSF and DOX delivered by the Co-NPs were found to have improved intracellular accumulation. Results of cytotoxicity assays showed that DSF/DOX delivered at the weight ratio of 0.5 and 1 could achieve a synergistic cytotoxic effect on breast cancer cell lines (MCF-7 and MDA-MB-231). In vivo imaging confirmed that the core–shell–corona nanoparticles could efficiently accumulate in tumors. In vivo anti-tumor effect results indicated that Co-NPs showed an improved drug synergistic effect on antitumor activity compared with the free drug combination. Therefore, it can be concluded that core–shell–corona nanoparticles prepared by PCL-b-PGlu-g-mPEG could be a promising co-delivery system for drug combination therapy in the treatment of breast cancer.

Graphical abstract: Synergistic breast tumor cell killing achieved by intracellular co-delivery of doxorubicin and disulfiram via core–shell–corona nanoparticles

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Publication details

The article was received on 07 Mar 2018, accepted on 17 May 2018 and first published on 22 May 2018


Article type: Paper
DOI: 10.1039/C8BM00271A
Biomater. Sci., 2018,6, 1869-1881

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    Synergistic breast tumor cell killing achieved by intracellular co-delivery of doxorubicin and disulfiram via core–shell–corona nanoparticles

    X. Tao, J. Gou, Q. Zhang, X. Tan, T. Ren, Q. Yao, B. Tian, L. Kou, L. Zhang and X. Tang, Biomater. Sci., 2018, 6, 1869
    DOI: 10.1039/C8BM00271A

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