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学科主题: 药学
题名:
The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells
作者: Wang, Xiao-Xing1; Li, Yang-Bing1; Yao, Hong-Juan1; Ju, Rui-Jun1; Zhang, Yan1; Li, Ruo-Jing1; Yu, Yang1; Zhang, Liang1; Lu, Wan-Liang1
关键词: DQA-PEG(2000)-DSPE conjugate ; Mitochondrial targeting resveratrol liposomes ; Mitochondria signaling pathway ; Intrinsic multidrug resistance ; Lung cancer
刊名: BIOMATERIALS
发表日期: 2011-08-01
DOI: 10.1016/j.biomaterials.2011.04.029
卷: 32, 期:24, 页:5673-5687
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]: MEMBRANE PERMEABILIZATION ; DRUG-RESISTANCE ; THERAPY ; CHEMOTHERAPY ; DELIVERY ; ACCUMULATION ; SPHEROIDS ; MECHANISM ; LEUKEMIA ; BINDING
英文摘要:

Intrinsic multidrug resistance (MDR) of cancers remains a major obstacle to successful chemotherapy. A dequalinium polyethylene glycol-distearoylphosphatidylethanolamine (DQA-PEG(2000)-DSPE) conjugate was synthesized as a mitochondriotropic molecule, and mitochondrial targeting resveratrol liposomes were developed by modifying DQA-PEC(2000)-DSPE on the surface of liposomes for overcoming the resistance. Evaluations were performed on the human lung adenocarcinoma A549 cells and resistant A549/cDDP cells, A549 and A549/cDDP tumor spheroids as well as the xenografted resistant A549/cDDP cancers in nude mice. The yield of DQA-PEC(2000)-DSPE conjugate synthesized was about 87% and the particle size of mitochondrial targeting resveratrol liposomes was approximately 70 nm. The mitochondrial targeting liposomes significantly enhanced the cellular uptake, and selectively accumulated into mitochondria when encapsulating coumarin as the fluorescent probe. Furthermore, mitochondrial targeting resveratrol liposomes induced apoptosis of both non-resistant and resistant cancer cells by dissipating mitochondria membrane potential, releasing cytochrome c and increasing the activities of caspase 9 and 3. They also exhibited significant antitumor efficacy in two kinds of cancer cells, in tumor spheroids by penetrating deeply into the core, and in xenografted resistant A549/cDDP cancers in nude mice. Mitochondrial targeting resveratrol liposomes co-treating with vinorelbine liposomes significantly enhanced the anticancer efficacy against the resistant A549/cDDP cells. In conclusion, mitochondrial targeting resveratrol liposomes would provide a potential strategy to treat the intrinsic resistant lung cancers by inducing apoptosis via mitochondria signaling pathway. (C) 2011 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 7091005 ; 2007CB935801
项目资助者: Beijing Natural Science Foundation ; National Basic Research Program of China (973 program)
WOS记录号: WOS:000292431100014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51471
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, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Xiao-Xing,Li, Yang-Bing,Yao, Hong-Juan,et al. The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells[J]. BIOMATERIALS,2011,32(24):5673-5687.
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