Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

Jinming Zhang,1,* Xiaobin Fang,1,* Zeyong Li,2 Hon Fai Chan,3 Zhixiu Lin,4 Yitao Wang,1 Meiwan Chen1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; 2Department of Laboratory Medicine, Guangdong No 2 Provincial...

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Autores principales:	Zhang J, Fang X, Li Z, Chan HF, Lin ZX, Wang Y, Chen M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Brusatol Redox-sensitive Pluronic® F68 Anticancer Disulfide linkage Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b96120bcee9742d9b94cc4f3b80d29ce
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spelling	oai:doaj.org-article:b96120bcee9742d9b94cc4f3b80d29ce2021-12-02T02:42:30ZRedox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol1178-2013https://doaj.org/article/b96120bcee9742d9b94cc4f3b80d29ce2018-02-01T00:00:00Zhttps://www.dovepress.com/redox-sensitive-micelles-composed-of-disulfide-linked-pluronic-linolei-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jinming Zhang,1,* Xiaobin Fang,1,* Zeyong Li,2 Hon Fai Chan,3 Zhixiu Lin,4 Yitao Wang,1 Meiwan Chen1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; 2Department of Laboratory Medicine, Guangdong No 2 Provincial People’s Hospital, Guangzhou, China; 3Department of Biomedical Engineering, Columbia University, New York, NY, USA; 4Faculty of Science, School of Chinese Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China *These authors contributed equally to this work Abstract: Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway. Keywords: poloxamer188, tumor micro-environment, glutathione, Brucea javanica, cancer treatmentZhang JFang XLi ZChan HFLin ZXWang YChen MDove Medical PressarticleBrusatolRedox-sensitivePluronic® F68AnticancerDisulfide linkageMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 939-956 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Brusatol Redox-sensitive Pluronic® F68 Anticancer Disulfide linkage Medicine (General) R5-920
spellingShingle	Brusatol Redox-sensitive Pluronic® F68 Anticancer Disulfide linkage Medicine (General) R5-920 Zhang J Fang X Li Z Chan HF Lin ZX Wang Y Chen M Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
description	Jinming Zhang,1,* Xiaobin Fang,1,* Zeyong Li,2 Hon Fai Chan,3 Zhixiu Lin,4 Yitao Wang,1 Meiwan Chen1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; 2Department of Laboratory Medicine, Guangdong No 2 Provincial People’s Hospital, Guangzhou, China; 3Department of Biomedical Engineering, Columbia University, New York, NY, USA; 4Faculty of Science, School of Chinese Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China *These authors contributed equally to this work Abstract: Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway. Keywords: poloxamer188, tumor micro-environment, glutathione, Brucea javanica, cancer treatment
format	article
author	Zhang J Fang X Li Z Chan HF Lin ZX Wang Y Chen M
author_facet	Zhang J Fang X Li Z Chan HF Lin ZX Wang Y Chen M
author_sort	Zhang J
title	Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
title_short	Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
title_full	Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
title_fullStr	Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
title_full_unstemmed	Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
title_sort	redox-sensitive micelles composed of disulfide-linked pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/b96120bcee9742d9b94cc4f3b80d29ce
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Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

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