Reduction-sensitive core-cross-linked mPEG-poly(ester-carbonate) micelles for glutathione-triggered intracellular drug release

doi:10.1039/c2py20240a

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	Reduction-sensitive core-cross-linked mPEG-poly(ester-carbonate) micelles for glutathione-triggered intracellular drug release
	Yan, Lesan 1,2; Wu, Wenbin 3; Zhao, Wei 1,2; Qi, Ruogu 1,2; Cui, Dongmei 1; Xie, Zhigang 1; Huang, Yubin 1; Tong, Ti 3; Jing, Xiabin 1
刊名	POLYMER CHEMISTRY
	2012
卷号	3 期号:9 页码:2403-2412
ISSN号	1759-9954
DOI	10.1039/c2py20240a
英文摘要	A functionalized six-membered cyclic carbonate monomer containing a protected thiol group, 2-(2,4-dinitrophenylthio)ethyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (MTC), was prepared. Ringopening polymerization (ROP) of MTC and L-lactide (LA) initiated by monohydroxyl poly(ethylene glycol) (mPEG) was successfully performed with controlled polymer molecular weight and molecular weight distribution. The structures of the obtained monomer and copolymers were confirmed by NMR and FTIR. After deprotection under mild conditions, the amphiphilic block copolymer was self-assembled into micelles in aqueous solution. By oxidation of the free thiol groups in the PMTC segments, the micelles with the cross-linked core were formed, and the enhanced stability against disruptive conditions was demonstrated by dynamic light scattering (DLS) measurement in the presence of DMF. Doxorubicin (DOX) was loaded into the micelles as a model drug. The in vitro DOX release behaviors indicated that cross-linking of the micelle cores resulted in a slow drug release and this process was greatly accelerated by adding glutathione (GSH) solution with comparable concentrations to intracellular levels in tumor cells. The cross-linked micelles were demonstrated to be efficiently internalized into the cells. Faster intracellular DOX release was observed by confocal laser scanning microscopy (CLSM) in the GSH pretreated MCF-7 cells than in the unpretreated MCF-7 cells. In vitro MTT assay revealed that the cross-linked micelles were biocompatible with L929 cells and MCF-7 cells. As expected, DOX-loaded cross-linked micelles showed higher cellular proliferation inhibition towards glutathione pretreated MCF-7 cells than that towards the unpretreated ones at various GSH concentrations. These results indicated that the bioreducible core-cross-linked micelles can be used as drug carriers for intelligent drug delivery.
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000306967600011
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/48905]
专题	中国科学院化学研究所
通讯作者	Jing, Xiabin
作者单位	1.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100039, Peoples R China 3.Jilin Univ, Second Hosp, Changchun 130041, Peoples R China
推荐引用方式 GB/T 7714	Yan, Lesan,Wu, Wenbin,Zhao, Wei,et al. Reduction-sensitive core-cross-linked mPEG-poly(ester-carbonate) micelles for glutathione-triggered intracellular drug release[J]. POLYMER CHEMISTRY,2012,3(9):2403-2412.
APA	Yan, Lesan.,Wu, Wenbin.,Zhao, Wei.,Qi, Ruogu.,Cui, Dongmei.,...&Jing, Xiabin.(2012).Reduction-sensitive core-cross-linked mPEG-poly(ester-carbonate) micelles for glutathione-triggered intracellular drug release.POLYMER CHEMISTRY,3(9),2403-2412.
MLA	Yan, Lesan,et al."Reduction-sensitive core-cross-linked mPEG-poly(ester-carbonate) micelles for glutathione-triggered intracellular drug release".POLYMER CHEMISTRY 3.9(2012):2403-2412.