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Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells
Wang, Zhipeng Tan, Jiao McConville, Christopher Kannappan, Vinodh Tawari Patricia Erebi Brown, James Ding, Jin Irache, Juan M. Mei, Qi-Bing
Wang, Zhipeng
Tan, Jiao
McConville, Christopher
Kannappan, Vinodh
Tawari Patricia Erebi
Brown, James
Ding, Jin
Irache, Juan M.
Mei, Qi-Bing
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2016-08-10
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Abstract
Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2 minutes to 7 hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.
Citation
Wang Z., Tan J., McConville C., Kannappan V., Tawari PE., Brown J., Ding J., Armesilla AL., Irache JM., Mei QB., Tan Y., Liu Y., Jiang W., Bian XW., Wang W. (2016) 'Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells', Nanomedicine: Nanotechnology, Biology and Medicine, 13 (2) pp. 641-657. doi: 10.1016/j.nano.2016.08.001
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Journal article
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en
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1549-9634