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Issue 42, 2016
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Development of a novel berberine-mediated mitochondria-targeting nano-platform for drug-resistant cancer therapy

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Abstract

Recent studies have shown that targeting doxorubicin to mitochondria of tumor cells can bypass the multi-drug resistance problem and inhibit tumor growth. We previously discovered that the C-9th and C-13th position-alkylated berberine derivatives possess improved mitochondria-targeting activity compared to berberine. Therefore, we hypothesize that these alkylated berberine derivatives could be utilized as potential mitochondrial-targeting ligands by inserting the alkyl chain into the liposomal bilayer membrane during the preparation of liposomes. In this research, a berberine derivate (a 16-carbon aliphatic chain was introduced to the C-9th of berberine, 9-C16 berberine) was employed to prepare mitochondria-targeting doxorubicin-loaded folic acid-conjugated polyethylene glycol(PEGylated) liposomes (MT-FOL-PLS). The results of in vitro cytotoxicity and apoptosis-inducing studies revealed that MT-FOL-PLS showed the strongest cytotoxicity and apoptosis-inducing effects in drug resistant MCF-7/adr cells in comparison with free doxorubicin and regular liposomal doxorubicin. MT-FOL-PLS enhanced cellular uptake of doxorubicin up to 15-fold compared to free doxorubicin, and targeted doxorubicin to mitochondria. In vivo and ex vivo drug distribution studies showed that MT-FOL-PLS increased the drug distribution in tumor and the administration of MT-FOL-PLS to resistant MCF-7/adr cell mouse xenografts stopped tumor growth. Our results confirmed that alkylated berberines can be exploited as mitochondrial-targeting ligands to overcome cancer multi-drug resistance, further advancing the research on active targeting of liposome delivery systems in the treatment of resistant cancer.

Graphical abstract: Development of a novel berberine-mediated mitochondria-targeting nano-platform for drug-resistant cancer therapy

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Publication details

The article was received on 11 Jul 2016, accepted on 26 Sep 2016 and first published on 26 Sep 2016


Article type: Paper
DOI: 10.1039/C6TB01730D
Citation: J. Mater. Chem. B, 2016,4, 6856-6864
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    Development of a novel berberine-mediated mitochondria-targeting nano-platform for drug-resistant cancer therapy

    J. Tuo, Y. Xie, J. Song, Y. Chen, Q. Guo, X. Liu, X. Ni, D. Xu, H. Huang, S. Yin, W. Zhu, J. Wu and H. Hu, J. Mater. Chem. B, 2016, 4, 6856
    DOI: 10.1039/C6TB01730D

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