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Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma
Yu, Yang; Wang, Zhao-Hui; Zhang, Liang; Yao, Hong-Juan; Zhang, Yan; Li, Ruo-Jing; Ju, Rui-Jun; Wang, Xiao-Xing; Zhou, Jia; Li, Nan; Lu, Wan-Liang1
关键词Mitochondrial targeting topotecan-loaded liposomes Multidrug resistance Metastases Breast cancer Melanoma
刊名BIOMATERIALS
2012-02-01
DOI10.1016/j.biomaterials.2011.10.085
33期:6页:1808-1820
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
资助者Beijing Natural Science Foundation ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National Natural Science Foundation of China
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]VITAMIN-E-TPGS ; IN-VITRO ; PERMEABILITY TRANSITION ; MULTIDRUG-RESISTANCE ; INDUCED APOPTOSIS ; P-GLYCOPROTEIN ; CELL-DEATH ; DEQUALINIUM ; LEUKEMIA ; MECHANISMS
英文摘要

Multidrug resistance and cancer metastases are two obstacles to a successful chemotherapy and metastases are closely associated with drug resistance. Mitochondrial targeting topotecan-loaded liposomes have been developed to overcome this resistance and resistance-related metastases. Investigations were performed on breast cancer MCF-7 and resistant MCF-7/adr cells, MCF-7 and resistant MCF-7/adr tumor spheroids, resistant MCF-7/adr cell xenografts in nude mice, and a naturally resistant B16 melanoma metastatic model in nude mice. The mitochondria] targeting topotecan-loaded liposomes were approximately 64 nm in size, and exhibited the strongest inhibitory effects on MCF-7 cells and resistant MCF-7/adr cells. Mitochondria] targeting effects were demonstrated by co-localization in mitochondria, enhanced drug content in mitochondria, dissipated mitochondrial membrane potential, opening of mitochondrial permeability transition pores, release of cytochrome C, and activation of caspase 9 and 3. The targeting liposomes had a stronger inhibitory effect on the resistant tumor spheroids in vitro, enhanced accumulation in resistant MCF-7/adr cell xenografts in mice, as well as being very effective on resistant MCF-7/adr cell xenografts in mice, and having a marked anti-metastastic effect on the naturally resistant B16 melanoma metastatic model in mice. In conclusion, mitochondrial targeting topotecan-loaded liposomes could be a promising strategy for treating resistant cancers and resistance-related metastases. (C) 2011 Elsevier Ltd. All rights reserved.

语种英语
所属项目编号7091005 ; 81172991
资助者Beijing Natural Science Foundation ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National Natural Science Foundation of China
WOS记录号WOS:000299986200013
引用统计
被引频次:38[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/400002259/65850
专题北京大学药学院
作者单位1.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Yu, Yang,Wang, Zhao-Hui,Zhang, Liang,et al. Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma[J]. BIOMATERIALS,2012,33(6):1808-1820.
APA Yu, Yang.,Wang, Zhao-Hui.,Zhang, Liang.,Yao, Hong-Juan.,Zhang, Yan.,...&Lu, Wan-Liang.(2012).Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma.BIOMATERIALS,33(6),1808-1820.
MLA Yu, Yang,et al."Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma".BIOMATERIALS 33.6(2012):1808-1820.
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