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学科主题: 药学
题名:
Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways
作者: Li, Nan1; Zhang, Cheng-Xiang1; Wang, Xiao-Xing1; Zhang, Liang1; Ma, Xu1; Zhou, Jia1; Ju, Rui-Jun1; Li, Xiu-Ying1; Zhao, Wei-Yu1; Lu, Wan-Liang1,2
关键词: Targeting lonidamine liposomes ; Drug-resistant lung cancer ; Mitochondrial signaling pathways ; Anticancer efficacy in mice
刊名: BIOMATERIALS
发表日期: 2013-04-01
DOI: 10.1016/j.biomaterials.2013.01.055
卷: 34, 期:13, 页:3366-3380
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 ; BREAST-CANCER ; LUNG-CANCER ; LOADED LIPOSOMES ; TUMOR-CELLS ; STEM-CELLS ; IN-VITRO ; CHEMOTHERAPY ; APOPTOSIS ; EPIRUBICIN
英文摘要:

Even when faced with elimination, functional materials may offer new alternatives to expensive drugs. Once used to treat benign prostate hypertrophy, the US Food and Drug Administration (FDA) suspended the use of lonidamine due to the occurrence of liver problems arising from its poor pharmaceutical properties. The objectives of the present study were to develop targeting lonidamine liposomes in combination with targeting epirubicin liposomes to circumvent drug-resistant cancer. Evaluations were performed on A549 and drug-resistant A549cDDP lung cancer cells and drug-resistant A549cDDP xenografted BALB/c nude mice. A DQA-PEG(2000)-DSPE conjugate was incorporated onto the liposomes as a targeting molecule. The constructed targeting lonidamine liposomes and targeting epirubicin liposomes measured were approximately 80 nm. The targeting lonidamine liposomes significantly enhanced the inhibitory effect of the targeting epirubicin liposomes in the drug-resistant A549cDDP cells in a lonidamine dose-dependent manner. Mechanism studies revealed that the targeting liposomes were selectively accumulated in the mitochondria, dissipating the mitochondrial membrane potential, opening the mitochondrial permeability transition pores, and releasing cytochrome C by translocation. This initiated a cascade of caspase 9 and 3 reactions and activated the pro-apoptotic Bax protein while suppressing the anti-apoptotic Mcl-1 protein, thereby enhancing the cytotoxic effect by acting on the mitochondrial signaling pathways. The efficacy in treating the drug-resistant A549cDDP xenografted tumor model after administration of the targeting lonidamine liposomes plus targeting epirubicin liposomes was the most significant compared with the administration of the controls at comparable doses. In conclusion, targeting lonidamine liposomes could be used as a potent co-therapy with an anticancer agent to enhance the efficacy of treating drug-resistant cancer by acting on the mitochondrial signaling pathways. (C) 2013 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 2009CB930300 ; 81172991 ; BMU20110263
项目资助者: National Key Science Research Program of China (973 program) ; National Science Foundation of China ; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (Tianjin Institute of Pharmaceutical Research) ; Innovation Team of Ministry of Education
WOS记录号: WOS:000316770100021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65034
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:
Li, Nan,Zhang, Cheng-Xiang,Wang, Xiao-Xing,et al. Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways[J]. BIOMATERIALS,2013,34(13):3366-3380.
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