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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

Authors Lin J, Zhao CY, Liu CJ, Fu SY, Han LY, Lu XP, Yang CR

Received 23 September 2017

Accepted for publication 7 December 2017

Published 7 February 2018 Volume 2018:13 Pages 805—830

DOI https://doi.org/10.2147/IJN.S152395

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


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

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