title: Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells.
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 2minutes to 7hours 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.
authors: Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK.
authors: Zhipeng
authors: Z
authors: Wang
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, China.
authors: Jiao
authors: J
authors: Tan
authors: School of Pharmacy, University of Birmingham, UK.
authors: Christopher
authors: C
authors: McConville
authors: Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK.
authors: Vinodh
authors: V
authors: Kannappan
authors: Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK.
authors: Patricia Erebi
authors: PE
authors: Tawari
authors: School of Life and Health Sciences and ARCHA, Aston University, UK.
authors: James
authors: J
authors: Brown
authors: Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
authors: Jin
authors: J
authors: Ding
authors: Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK.
authors: Angel L
authors: AL
authors: Armesilla
authors: School of Pharmacy, University of Navarra, Pamplona, Spain.
authors: Juan M
authors: JM
authors: Irache
authors: School of Pharmacy, Fourth Military Medical University, China.
authors: Qi-Bing
authors: QB
authors: Mei
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, China.
authors: Yuhuan
authors: Y
authors: Tan
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, China.
authors: Ying
authors: Y
authors: Liu
authors: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
authors: Wenguo
authors: W
authors: Jiang
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, China; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University, Guangzhou, China. Electronic address: bianxiuwu@263.net.
authors: Xiu-Wu
authors: XW
authors: Bian
authors: Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK. Electronic address: w.wang2@wlv.ac.uk.
authors: Weiguang
authors: W
authors: Wang
mesh_terms: D065086:Acetaldehyde Dehydrogenase Inhibitors / Q000008:administration & dosage*; D000818:Animals; D004221:Disulfiram / Q000008:administration & dosage*; D004337:Drug Carriers; D006018:Glycols; D006801:Humans; D019344:Lactic Acid; D008113:Liver Neoplasms / Q000188:drug therapy*; D053758:Nanoparticles; D011100:Polyglycolic Acid
chemical_list: D065086:Acetaldehyde Dehydrogenase Inhibitors; D004337:Drug Carriers; D006018:Glycols; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004221:Disulfiram
keywords: Cancer stem cells; Disulfiram; Drug delivery; Drug repositioning; Liver cancer; Nano-technology; PLGA