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Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol
Zhane, Jinming1; Fang, Xiaobin1; Li, Zeyong2; Chan, Hon Fai3; Lin, Zhixiu4; Wang, Yitao1; Chen, Meiwan1
2018
Source PublicationINTERNATIONAL JOURNAL OF NANOMEDICINE
ISSN1178-2013
Volume13Pages:939-956
Abstract

Brusatol (Bru) exhibits promising anticancer c fleas, 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 (R) F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by H-1-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 internalisation, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway.

KeywordPoloxamer188 Tumor Micro-environment Glutathione Brucea Javanica Cancer Treatment
DOIhttp://doi.org/10.2147/IJN.S130696
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics ; Pharmacology & Pharmacy
WOS SubjectNanoscience & Nanotechnology ; Pharmacology & Pharmacy
WOS IDWOS:000425320800002
PublisherDOVE MEDICAL PRESS LTD
The Source to ArticleWOS
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
2.Department of Laboratory Medicine, Guangdong No 2 Provincial People’s Hospital, Guangzhou, China
3.Department of Biomedical Engineering, Columbia University, New York, NY, USA
4.Faculty of Science, School of Chinese Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhane, Jinming,Fang, Xiaobin,Li, Zeyong,et al. Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2018,13:939-956.
APA Zhane, Jinming.,Fang, Xiaobin.,Li, Zeyong.,Chan, Hon Fai.,Lin, Zhixiu.,...&Chen, Meiwan.(2018).Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol.INTERNATIONAL JOURNAL OF NANOMEDICINE,13,939-956.
MLA Zhane, Jinming,et al."Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol".INTERNATIONAL JOURNAL OF NANOMEDICINE 13(2018):939-956.
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