Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance

Kai Dong,1 Yan Yan,2 Pengchong Wang,2 Xianpeng Shi,2 Lu Zhang,2 Ke Wang,2 Jianfeng Xing,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s...

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Autores principales:	Dong K, Yan Y, Wang PC, Shi XP, Zhang L, Wang K, Xing JF, Dong YL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Multidrug resistance Reduction-sensitive Disulfide bond TPGS Paclitaxel Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/04a19a94f6124b6a825e9e88d9238845
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spelling	oai:doaj.org-article:04a19a94f6124b6a825e9e88d92388452021-12-02T01:35:23ZBiodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance1178-2013https://doaj.org/article/04a19a94f6124b6a825e9e88d92388452016-10-01T00:00:00Zhttps://www.dovepress.com/biodegradable-mixed-mpeg-ss-2satpgs-micelles-for-triggered-intracellul-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kai Dong,1 Yan Yan,2 Pengchong Wang,2 Xianpeng Shi,2 Lu Zhang,2 Ke Wang,2 Jianfeng Xing,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Abstract: In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (D-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA). The structure of the obtained polymer was similar to poly (ethylene glycol)-phosphatidylethanolamine (PEG-PE). Then the mixed micelles, MPEG-SS-2SA/TPGS, were prepared by MPEG-SS-2SA and TPGS through the thin film hydration method and loaded paclitaxel (PTX) as the model drug. The in vitro release study revealed that the mixed micelles could rapidly release PTX within 24 h under a reductive environment because of the breaking of disulfide bonds. In cell experiments, the mixed micelles significantly inhibited the activity of mitochondrial respiratory complex II, also reduced the mitochondrial membrane potential, and the content of adenosine triphosphate, thus effectively inhibiting the efflux of PTX from cells. Moreover, in the confocal laser scanning microscopy, cellular uptake and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, the MPEG-SS-2SA/TPGS micelles achieved faster release and more uptake of PTX in Michigan Cancer Foundation-7/PTX cells and showed better antitumor effects as compared with the insensitive control. In conclusion, the biodegradable mixed micelles, MPEG-SS-2SA/TPGS, could be potential vehicles for delivering hydrophobic chemotherapeutic drugs in MDR cancer therapy. Keywords: reversal of multidrug resistance, reduction-sensitive, disulfide bond, mixed micelles, MCF-7/PTX cellsDong KYan YWang PCShi XPZhang LWang KXing JFDong YLDove Medical PressarticleMultidrug resistanceReduction-sensitiveDisulfide bondTPGSPaclitaxelMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5109-5123 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Multidrug resistance Reduction-sensitive Disulfide bond TPGS Paclitaxel Medicine (General) R5-920
spellingShingle	Multidrug resistance Reduction-sensitive Disulfide bond TPGS Paclitaxel Medicine (General) R5-920 Dong K Yan Y Wang PC Shi XP Zhang L Wang K Xing JF Dong YL Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
description	Kai Dong,1 Yan Yan,2 Pengchong Wang,2 Xianpeng Shi,2 Lu Zhang,2 Ke Wang,2 Jianfeng Xing,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Abstract: In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (D-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA). The structure of the obtained polymer was similar to poly (ethylene glycol)-phosphatidylethanolamine (PEG-PE). Then the mixed micelles, MPEG-SS-2SA/TPGS, were prepared by MPEG-SS-2SA and TPGS through the thin film hydration method and loaded paclitaxel (PTX) as the model drug. The in vitro release study revealed that the mixed micelles could rapidly release PTX within 24 h under a reductive environment because of the breaking of disulfide bonds. In cell experiments, the mixed micelles significantly inhibited the activity of mitochondrial respiratory complex II, also reduced the mitochondrial membrane potential, and the content of adenosine triphosphate, thus effectively inhibiting the efflux of PTX from cells. Moreover, in the confocal laser scanning microscopy, cellular uptake and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, the MPEG-SS-2SA/TPGS micelles achieved faster release and more uptake of PTX in Michigan Cancer Foundation-7/PTX cells and showed better antitumor effects as compared with the insensitive control. In conclusion, the biodegradable mixed micelles, MPEG-SS-2SA/TPGS, could be potential vehicles for delivering hydrophobic chemotherapeutic drugs in MDR cancer therapy. Keywords: reversal of multidrug resistance, reduction-sensitive, disulfide bond, mixed micelles, MCF-7/PTX cells
format	article
author	Dong K Yan Y Wang PC Shi XP Zhang L Wang K Xing JF Dong YL
author_facet	Dong K Yan Y Wang PC Shi XP Zhang L Wang K Xing JF Dong YL
author_sort	Dong K
title	Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
title_short	Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
title_full	Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
title_fullStr	Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
title_full_unstemmed	Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
title_sort	biodegradable mixed mpeg-ss-2sa/tpgs micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/04a19a94f6124b6a825e9e88d9238845
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Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance

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