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

Zhipeng Wang, Jiao Tan, Christopher McConville, 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

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages641-657
Number of pages17
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number2
Early online date10 Aug 2016
DOIs
Publication statusPublished - Feb 2017

Fingerprint

Disulfiram
Neoplastic Stem Cells
Liver Neoplasms
Liver
Acids
Oncology
Cytotoxicity
Encapsulation
Half-Life
polylactic acid-polyglycolic acid copolymer
Milk
Stem cells
Fluorouracil
Copper
Pharmaceutical Preparations
Alcoholism
Degradation
Neoplasms

Bibliographical note

© 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/).

Keywords

  • disulfiram
  • PLGA
  • liver cancer
  • cancer stem cells
  • drug repositioning
  • nano-technology
  • drug delivery

Cite this

Wang, Z., Tan, J., McConville, C., Kannappan, V., Erebi Tawari, P., Brown, J., ... Wang, W. (2017). Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells. 13(2), 641-657. https://doi.org/10.1016/j.nano.2016.08.001
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 ; Wang, Weiguang. / Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells. 2017 ; Vol. 13, No. 2. pp. 641-657.
@article{229e7f2982674eb786206789c747de61,
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 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.",
keywords = "disulfiram, PLGA, liver cancer, cancer stem cells, drug repositioning, nano-technology, drug delivery",
author = "Zhipeng Wang and Jiao Tan and Christopher McConville and Vinodh Kannappan and {Erebi Tawari}, Patricia and James Brown and Jin Ding and Armesilla, {Angel L.} and Irache, {Juan M.} and Qi-Bing Mei and Yuhuan Tan and Ying Liu and Wenguo Jiang and Xiuwu Bian and Weiguang Wang",
note = "{\circledC} 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/).",
year = "2017",
month = "2",
doi = "10.1016/j.nano.2016.08.001",
language = "English",
volume = "13",
pages = "641--657",
number = "2",

}

Wang, Z, Tan, J, McConville, C, Kannappan, V, Erebi Tawari, P, Brown, J, Ding, J, Armesilla, AL, Irache, JM, Mei, Q-B, Tan, Y, Liu, Y, Jiang, W, Bian, X & Wang, W 2017, 'Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells' vol. 13, no. 2, pp. 641-657. https://doi.org/10.1016/j.nano.2016.08.001

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; Wang, Weiguang.

Vol. 13, No. 2, 02.2017, p. 641-657.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells

AU - Wang, Zhipeng

AU - Tan, Jiao

AU - McConville, Christopher

AU - Kannappan, Vinodh

AU - Erebi Tawari, Patricia

AU - Brown, James

AU - Ding, Jin

AU - Armesilla, Angel L.

AU - Irache, Juan M.

AU - Mei, Qi-Bing

AU - Tan, Yuhuan

AU - Liu, Ying

AU - Jiang, Wenguo

AU - Bian, Xiuwu

AU - Wang, Weiguang

N1 - © 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/).

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

KW - disulfiram

KW - PLGA

KW - liver cancer

KW - cancer stem cells

KW - drug repositioning

KW - nano-technology

KW - drug delivery

UR - http://www.scopus.com/inward/record.url?scp=85010377794&partnerID=8YFLogxK

U2 - 10.1016/j.nano.2016.08.001

DO - 10.1016/j.nano.2016.08.001

M3 - Article

VL - 13

SP - 641

EP - 657

IS - 2

ER -