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学科主题: 药学
题名:
The anticancer efficacy of paclitaxel liposomes modified with mitochondrial targeting conjugate in resistant lung cancer
作者: Zhou, Jia1; Zhao, Wei-Yu1; Ma, Xu1; Ju, Rui-Jun1; Li, Xiu-Ying1; Li, Nan1; Sun, Meng-Ge1; Shi, Ji-Feng1; Zhang, Cheng-Xiang1; Lu, Wan-Liang1,2
关键词: TPGS(1000)-TPP conjugate ; Targeting paclitaxel liposomes ; Mitochondrial signaling pathway ; Resistant lung cancer ; Anticancer efficacy
刊名: BIOMATERIALS
发表日期: 2013-05-01
DOI: 10.1016/j.biomaterials.2013.01.078
卷: 34, 期:14, 页:3626-3638
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]: VITAMIN-E-TPGS ; HUMAN NEUROBLASTOMA-CELLS ; CYTOCHROME-C RELEASE ; POLYETHYLENE-GLYCOL ; IN-VITRO ; DRUG-DELIVERY ; APOPTOSIS ; NANOPARTICLES ; CYTOTOXICITY ; MECHANISM
英文摘要:

Lung cancer is the leading cause of cancer-related death in humans and the multidrug resistance (MDR) is the major obstacle to successful chemotherapy of lung cancer. In this study, a D-alpha-tocopheryl polyethylene glycol 1000 succinate-triphenylphosphine conjugate (TPGS(1000)-TPP) was synthesized as the mitochondrial targeting molecule, and was incorporated onto the surface of paclitaxel liposomes to treat the drug-resistant lung cancer. Evaluations were performed on the human lung cancer A549 cells, the drug-resistant lung cancer A549/cDDP cells, and the drug-resistant lung cancer A549/cDDP cells xenografted nude mice. The yield of TPGS(1000)-TPP conjugate synthesized was about 50% and the particle size of targeting paclitaxel liposomes developed was approximately 80 nm. In comparison with taxol and regular paclitaxel liposomes, the targeting paclitaxel liposomes exhibited the strongest anticancer efficacy in vitro and in the drug-resistant A549/cDDP xenografted tumor model. The targeting paclitaxel liposomes could significantly enhance the cellular uptake, be selectively accumulated into the mitochondria, and cause the release of cytochrome C. This targeting delivery of drug initiated a cascade of caspase 9 and 3 reactions, activated the pro-apoptotic Bax and Bid proteins and suppressed the antiapoptotic Bcl-2 protein, thereby enhancing the apoptosis by acting on the mitochondrial signaling pathways. In conclusion, the targeting paclitaxel liposomes have the potential to treat drug-resistant lung cancer. (C) 2013 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 2013CB932501 ; 81172991 ; BMU20110263
项目资助者: National Basic Research Program of China (973 program) ; Grant of National Science Foundation of China ; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (Tianjin Institute of Pharmaceutical Research) ; Grant for Innovation Team of Ministry of Education
WOS记录号: WOS:000317534200009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61394
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, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Tianjin Inst Pharmaceut Res, State Key Lab Drug Delivery Technol & Pharmacokin, Tianjin 300193, Peoples R China

Recommended Citation:
Zhou, Jia,Zhao, Wei-Yu,Ma, Xu,et al. The anticancer efficacy of paclitaxel liposomes modified with mitochondrial targeting conjugate in resistant lung cancer[J]. BIOMATERIALS,2013,34(14):3626-3638.
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