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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, Armesilla, Angel L., Irache, Juan M., Mei, Qi-Bing, Tan, Yuhuan, Liu, Ying, Jiang, Wen Guo, 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. 10.1016/j.nano.2016.08.001

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Disulfiram; PLGA; liver cancer; cancer stem cells; drug repositioning; nano-technology; drug delivery
Publisher: Elsevier
ISSN: 1549-9634
Date of First Compliant Deposit: 21 February 2017
Date of Acceptance: 1 August 2016
Last Modified: 04 Jun 2017 09:21
URI: http://orca-mwe.cf.ac.uk/id/eprint/93839

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