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

Research output: Contribution to journalArticlepeer-review

Authors

  • Zhipeng Wang
  • Jiao Tan
  • Vinodh Kannappan
  • Patricia Erebi Tawari
  • James Brown
  • Jin Ding
  • Angel L. Armesilla
  • Juan M. Irache
  • Qi-bing Mei
  • Yuhuan Tan
  • Ying Liu
  • Wenguo Jiang
  • Xiuwu Bian
  • Weiguang Wang

Colleges, School and Institutes

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 hin 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.

Details

Original languageEnglish
Pages (from-to)641-657
Number of pages17
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume13
Issue number2
Early online date10 Aug 2016
Publication statusPublished - Feb 2017

Keywords

  • Disulfiram, PLGA, Liver cancer, Cancer stem cells, Drug repositioning, Nano-technology, Drug delivery