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The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells
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
2011-08-01
DOI10.1016/j.biomaterials.2011.04.029
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
WOS记录号WOS:000292431100014
引用统计
被引频次:85[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51471
专题北京大学药学院
北京大学第二临床医学院_麻醉科
北京大学第三临床医学院_麻醉科
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
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GB/T 7714
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.
APA Wang, Xiao-Xing.,Li, Yang-Bing.,Yao, Hong-Juan.,Ju, Rui-Jun.,Zhang, Yan.,...&Lu, Wan-Liang.(2011).The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells.BIOMATERIALS,32(24),5673-5687.
MLA Wang, Xiao-Xing,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".BIOMATERIALS 32.24(2011):5673-5687.
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