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学科主题: 药学
题名:
Materializing sequential killing of tumor vasculature and tumor cells via targeted polymeric micelle system
作者: Wang, Yiguang1; Yang, Tingyuan1; Wang, Xun1; Dai, Wenbing1; Wang, Jiancheng1; Zhang, Xuan1; Li, Zaiquan2; Zhang, Qiang1
关键词: Targeted polymeric micelles ; Doxorubicin ; Combretastatin A4 ; Combination tumor therapy ; Antivascular therapy
刊名: JOURNAL OF CONTROLLED RELEASE
发表日期: 2011-02-10
DOI: 10.1016/j.jconrel.2010.10.027
卷: 149, 期:3, 页:299-306
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: PHASE-II TRIAL ; COMBRETASTATIN A-4 ; CREMOPHOR-FREE ; GENEXOL-PM ; CANCER-THERAPY ; DRUG-DELIVERY ; LUNG-CANCER ; DOXORUBICIN ; PACLITAXEL ; CHEMOTHERAPY
英文摘要:

The purpose of this study was to develop a targeted combinatorial polymeric micelle system that can sequentially kill tumor vasculature and tumor cells and increase the anticancer efficacy. Toward this goal, alpha v beta 3 integrin-targeting peptide (RGD) functionalized polymeric micelles (RFPMs) based on the use of poly (ethylene glycol)-b-poly(d.1-lactide) (PEG-PLA) was developed. Doxorubicin was conjugated to the biodegradable PEG-PLA micelle core, and combretastatin A4 was physically encapsulated into micelles (RFPMs-DOX-CA4). The RFPM5-DOX-CA4 has a particle size of 29.2 +/- 2.5 nm with spherical shape and high encapsulation efficiency for both drugs (> 95%). The micelles exhibited sequential release kinetics for both drugs. Treatment with RFPM5-DOX-CA4 resulted in the sequential killing of endothelial cells and tumor cells in vitro. RFPMs displayed prolonged circulation time and more drug accumulation in solid tumor than unfunctionalized polymeric micelles (UFPMs). In B16-F10 tumor-bearing mice, RFPMs-DOX-CA4 showed stronger tumor growth inhibition and significantly higher survival rate compared with the other treatment groups. Treatment with RFPMs-DOX-CA4 caused a dramatic destruction of tumor vasculature and reduction of tumor cell proliferation in vivo. These results suggested that the integrated strategy can be exploited as a potential treatment modality for cancer. (C) 2010 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2009CB930300 ; 30772666 ; 2007AA021811
项目资助者: The National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; National High-Tech R&amp ; D Program (863 Program) ; Ministry of Education
WOS记录号: WOS:000288722800012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52125
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
2.Peking Univ, Dept Biochem & Mol Biol, Sch Basic Med Sci, Beijing 100083, Peoples R China

Recommended Citation:
Wang, Yiguang,Yang, Tingyuan,Wang, Xun,et al. Materializing sequential killing of tumor vasculature and tumor cells via targeted polymeric micelle system[J]. JOURNAL OF CONTROLLED RELEASE,2011,149(3):299-306.
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