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

International Journal of Nanomedicine
Jinming ZhangMeiwan Chen

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 ant...Continue Reading

Citations

Jan 18, 2020·Future Medicinal Chemistry·Hongzhi LinHaopeng Sun
Jul 18, 2021·Colloids and Surfaces. B, Biointerfaces·Tais Monteiro MagneRalph Santos-Oliveira
Aug 6, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yihenew Simegniew Birhan, Hsieh-Chih Tsai

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Methods Mentioned

BETA
amidation
dynamic light scattering
transmission electron microscopy
protein assay
flow cytometry
nuclear magnetic resonance
Fluorescence

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