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学科主题: 药学
题名:
Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma
作者: 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
发表日期: 2012-02-01
DOI: 10.1016/j.biomaterials.2011.10.085
卷: 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
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
项目资助者: Beijing Natural Science Foundation ; National Natural Science Foundation of China
WOS记录号: WOS:000299986200013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65850
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, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
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.
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