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

doi:10.1016/j.nano.2016.08.001

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 journal › Article › peer-review

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.

Original language	English
Pages (from-to)	641-657
Number of pages	17
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	13
Issue number	2
Early online date	10 Aug 2016
DOIs	https://doi.org/10.1016/j.nano.2016.08.001
Publication status	Published - Feb 2017

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

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10.1016/j.nano.2016.08.001Licence: CC BY-NC-ND 3.0

Disulfiram to target liver cancer stem-like cells
© 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/).
Final published version, 3.08 MBLicence: CC BY-NC-ND 3.0

Cite this

Wang, Z., Tan, J., McConville, C., Kannappan, V., Erebi Tawari, P., Brown, J., Ding, J., Armesilla, A. L., Irache, J. M., 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. Nanomedicine: Nanotechnology, Biology, and Medicine, 13(2), 641-657. https://doi.org/10.1016/j.nano.2016.08.001

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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 = "{\textcopyright} 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/).",

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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', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 13, no. 2, pp. 641-657. https://doi.org/10.1016/j.nano.2016.08.001

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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

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.

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KW - PLGA

KW - liver cancer

KW - cancer stem cells

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KW - nano-technology

KW - drug delivery

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DO - 10.1016/j.nano.2016.08.001

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SN - 1549-9634

VL - 13

SP - 641

EP - 657

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

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