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学科主题: 药学
题名:
The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
作者: Men, Ying1; Wang, Xiao-Xing1; Li, Ruo-Jing1; Zhang, Yan1; Tian, Wei1; Yao, Hong-Juan1; Ju, Rui-Jun1; Ying, Xue1; Zhou, Jia1; Li, Nan1; Zhang, Liang1; Yu, Yang1; Lu, Wan-Liang1
关键词: mitosomes ; mitochondria signaling pathway ; nude mice
刊名: INTERNATIONAL JOURNAL OF NANOMEDICINE
发表日期: 2011
DOI: 10.2147/IJN.S24847
卷: 6, 页:3125-3137
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
研究领域[WOS]: Science & Technology - Other Topics ; Pharmacology & Pharmacy
关键词[WOS]: CANCER-CHEMOTHERAPY ; DRUG-DELIVERY ; CYTOCHROME-C ; APOPTOSIS ; GENE ; GROWTH ; CELLS ; MICE ; PHOSPHORYLATION ; ACTIVATION
英文摘要:

Background: Multidrug resistance (MDR) of cancers can be circumvented by inducing programmed cell death, which is known as apoptosis. Mitochondria play a crucial role in apoptosis. Mitochondria-specific therapy would provide an efficient strategy for treating resistant cancers.

Design and methods: A strategy was proposed here to overcome MDR by designing cancer mitochondria-specific drug-loaded liposomes, namely, antiresistant epirubicin mitosomes, aimed at treating resistant leukemia by targeting mitochondria. Evaluations were performed on human chronic leukemia K562, MDR K562/ADR cells, and female BALB/c nude mice xenografted with MDR K562/ADR cells. The liposomes were characterized through assays of cytotoxicity, mitochondrial targeting, caspase-9 and caspase-3, antitumor activities, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis.

Results: The average size of antiresistant epirubicin mitosomes was in the range of 105-115 nm. Antiresistant epirubicin mitosomes were effective in inhibiting proliferation of MDR K562/ADR cells in vitro and selectively accumulated into the mitochondria. Caspase-9 and caspase-3 activity was increased after applying antiresistant epirubicin mitosomes. In xenografted resistant MDR K562/ADR tumor in nude mice, antiresistant tumor effect of antiresistant epirubicin mitosomes was evidently observed. Apoptotic inducing effects by antiresistant epirubicin mitosomes were noticeably evidenced via mitochondrial pathway.

Conclusions: Antiresistant epirubicin mitosomes had significant inhibitory effect against resistant leukemia in vitro and in vivo, hence providing a promising strategy for improving therapeutic efficacy in resistant human leukemia.

语种: 英语
所属项目编号: 7091005 ; 81172991 ; 2009CB930300
项目资助者: Beijing Natural Science Foundation ; National Natural Science Foundation of China ; National Key Science Research Program of China (973 program)
WOS记录号: WOS:000297694100001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51541
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Men, Ying,Wang, Xiao-Xing,Li, Ruo-Jing,et al. The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2011,6:3125-3137.
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