Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells

Wang, Zhipeng, Tan, Jiao, McConville, Christopher, Kannappan, Vinodh, Erebi Tawari, Patricia, Brown, James, Ding, Jin, Armesilla, Angel L., Irache, Juan M., Mei, Qi-Bing, Tan, Yuhuan, Liu, Ying, Jiang, Wenguo, Bian, Xiuwu and Wang, Weiguang (2017). 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.

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.

Publication DOI: https://doi.org/10.1016/j.nano.2016.08.001
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences > Cell & Tissue Biomedical Research
Additional Information: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Uncontrolled Keywords: disulfiram,PLGA,liver cancer,cancer stem cells,drug repositioning,nano-technology,drug delivery,Medicine (miscellaneous),Bioengineering,Biomedical Engineering,Molecular Medicine,Materials Science(all),Pharmaceutical Science
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2017-02
Authors: Wang, Zhipeng
Tan, Jiao
McConville, Christopher
Kannappan, Vinodh
Erebi Tawari, Patricia
Brown, James ( 0000-0002-3504-7373)
Ding, Jin
Armesilla, Angel L.
Irache, Juan M.
Mei, Qi-Bing
Tan, Yuhuan
Liu, Ying
Jiang, Wenguo
Bian, Xiuwu
Wang, Weiguang

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