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学科主题: 药学
题名:
pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) for tumor-targeting and controlled delivery of doxorubicin and P-glycoprotein inhibitor
作者: Zhao, Yong; Zhou, Yanxia; Wang, Dishi; Gao, Yajie; Li, Jinwen; Ma, Shujin; Zhao, Lei; Zhang, Chao; Liu, Yan; Li, Xinru
关键词: Poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) ; pH-responsive polymeric micelle ; Folate-targeted delivery ; P-glycoprotein inhibitor ; Multidrug resistance
刊名: ACTA BIOMATERIALIA
发表日期: 2015-04-15
DOI: 10.1016/j.actbio.2015.01.010
卷: 17, 页:182-192
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]: Engineering ; Materials Science
关键词[WOS]: OVERCOMING MULTIDRUG-RESISTANCE ; COPOLYMER MICELLES ; TRANSPORT MECHANISM ; CYCLOSPORINE-A ; CELL LINES ; IN-VITRO ; DRUG ; NANOPARTICLES ; PACLITAXEL ; BARRIER
英文摘要:

The combination of a chemotherapeutic drug with a P-glycoprotein (P-gp) inhibitor has emerged as a promising strategy for treating multidrug resistance (MDR) cancer. To ensure that two drugs can be co-delivered to the tumor region and quickly released in tumor cells, tumor-targeted and pH-sensitive polymeric micelles were designed and prepared by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline (EOz) with anionic ring-opening polymerization of D,L-lactide (LA), and then encapsulating doxorubicin (DOX) and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) into the micelles self-assembled by poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) and DSPE-PEG-folate. PEOz-PLA exhibited a low critical micelle concentration and negligible cytotoxicity. The micelles enabled the rapid release of DOX when pH decreased from 7.4 to 5.0. The targeting ability of the micelles was demonstrated by in vitro flow cytometry in KBv cells and in vivo real time near-infrared fluorescence imaging in KBv tumor-bearing nude mice. The efficiency of MDR reversion for the micelles was testified by enhancement of intracellular DOX accumulation and cytotoxicity. The efficient drug delivery by the micelles was attributed to synergistic effects of folate-mediated targeting, pH-triggered drug release and TPGS1000-aroused P-gp inhibition. Therefore, the designed multifunctional polymeric micelles may have significant promise for therapeutic application of MDR cancer. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81172990 ; 2015CB932100 ; BMU20110263
项目资助者: National Natural Science Foundation of China ; National Key Science Research Program of China (973 Program) ; Ministry of Education
WOS记录号: WOS:000352665700018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57938
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China

Recommended Citation:
Zhao, Yong,Zhou, Yanxia,Wang, Dishi,et al. pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) for tumor-targeting and controlled delivery of doxorubicin and P-glycoprotein inhibitor[J]. ACTA BIOMATERIALIA,2015,17:182-192.
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