Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Jing Lin,* Chaoyue Zhao,* Cuijuan Liu, Shiyao Fu, Luying Han, Xinping Lu, Chunrong Yang College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China *These authors contributed equally to this work Introduction: The development of nanodrug carriers utilizing tumor microenvironment has bec...

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Autores principales: Lin J, Zhao CY, Liu CJ, Fu SY, Han LY, Lu XP, Yang CR
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
Redox-responsive
Mixed micelles
Multidrug resistance
Paclitaxel
Tumor microenvironment
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/0f57981d6b464699ba5467886ce58e0d
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spelling oai:doaj.org-article:0f57981d6b464699ba5467886ce58e0d2021-12-02T09:02:15ZRedox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors1178-2013https://doaj.org/article/0f57981d6b464699ba5467886ce58e0d2018-02-01T00:00:00Zhttps://www.dovepress.com/redox-responsive-f127-folatef127-disulfide-bond-d-alpha-tocopheryl-pol-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jing Lin,* Chaoyue Zhao,* Cuijuan Liu, Shiyao Fu, Luying Han, Xinping Lu, Chunrong Yang College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China *These authors contributed equally to this work Introduction: The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR). Materials and methods: This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and D-α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA, and Pluronic P123, were prepared to load paclitaxel (PTX). Results: The in vitro release study demonstrated that FFSSTP/PTX accelerated the PTX release through the breakage of disulfide bond in reductive environment. In cellular experiment, FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping out PTX by interfering with the mitochondrial function and ATP synthesis. Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular levels of ROS. Conclusion: FFSSTP could become a potential carrier for the treatment of MDR tumors. Keywords: redox responsive, mixed micelles, multidrug resistance, paclitaxel, tumor microenvironmentLin JZhao CYLiu CJFu SYHan LYLu XPYang CRDove Medical PressarticleRedox-responsiveMixed micellesMultidrug resistancePaclitaxelTumor microenvironmentMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 805-830 (2018)
institution DOAJ
collection DOAJ
language EN
topic Redox-responsive
Mixed micelles
Multidrug resistance
Paclitaxel
Tumor microenvironment
Medicine (General)
R5-920
spellingShingle Redox-responsive
Mixed micelles
Multidrug resistance
Paclitaxel
Tumor microenvironment
Medicine (General)
R5-920
Lin J
Zhao CY
Liu CJ
Fu SY
Han LY
Lu XP
Yang CR
Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
description Jing Lin,* Chaoyue Zhao,* Cuijuan Liu, Shiyao Fu, Luying Han, Xinping Lu, Chunrong Yang College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China *These authors contributed equally to this work Introduction: The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR). Materials and methods: This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and D-α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA, and Pluronic P123, were prepared to load paclitaxel (PTX). Results: The in vitro release study demonstrated that FFSSTP/PTX accelerated the PTX release through the breakage of disulfide bond in reductive environment. In cellular experiment, FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping out PTX by interfering with the mitochondrial function and ATP synthesis. Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular levels of ROS. Conclusion: FFSSTP could become a potential carrier for the treatment of MDR tumors. Keywords: redox responsive, mixed micelles, multidrug resistance, paclitaxel, tumor microenvironment
format article
author Lin J
Zhao CY
Liu CJ
Fu SY
Han LY
Lu XP
Yang CR
author_facet Lin J
Zhao CY
Liu CJ
Fu SY
Han LY
Lu XP
Yang CR
author_sort Lin J
title Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
title_short Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
title_full Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
title_fullStr Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
title_full_unstemmed Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
title_sort redox-responsive f127-folate/f127-disulfide bond-d-α-tocopheryl polyethylene glycol 1000 succinate/p123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/0f57981d6b464699ba5467886ce58e0d
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AT luxp redoxresponsivef127folatef127disulfidebonddalphatocopherylpolyethyleneglycol1000succinatep123mixedmicellesloadedwithpaclitaxelforthereversalofmultidrugresistanceintumors
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