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Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways
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
2013-04-01
DOI10.1016/j.biomaterials.2013.01.055
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
WOS记录号WOS:000316770100021
项目编号2009CB930300 ; 81172991 ; BMU20110263
资助机构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
引用统计
被引频次:37[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/400002259/65034
专题北京大学药学院
医学人文研究院/公共教学部_哲学与社会科学系
北京大学第一临床医学院_检验科
北京大学第三临床医学院_麻醉科
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
推荐引用方式
GB/T 7714
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.
APA Li, Nan.,Zhang, Cheng-Xiang.,Wang, Xiao-Xing.,Zhang, Liang.,Ma, Xu.,...&Lu, Wan-Liang.(2013).Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways.BIOMATERIALS,34(13),3366-3380.
MLA Li, Nan,et al."Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways".BIOMATERIALS 34.13(2013):3366-3380.
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