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已发表论文

氧化还原反应性 F127-叶酸/F127-二硫键接-D-α-生育酚聚乙二醇 1000 琥珀酸酯/P123 的混合胶束(负载紫杉醇)用于逆转肿瘤中的多药物抗性

 

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

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