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学科主题: 药学
题名:
A Combination of Targeted Sunitinib Liposomes and Targeted Vinorelbine Liposomes for Treating Invasive Breast Cancer
作者: Shi, Ji-Feng; Sun, Meng-Ge; Li, Xiu-Ying; Zhao, Yao; Ju, Rui-Jun; Mu, Li-Min; Yan, Yan; Li, Xue-Tao; Zeng, Fan; Lu, Wan-Liang
关键词: Targeted Sunitinib Liposomes ; Targeted Vinorelbine Liposomes ; Indicators for Vasculogenic Mimicry Channels ; Caspase ; Invasive Breast Cancer ; Anticancer Efficacy
刊名: JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
发表日期: 2015-09-01
DOI: 10.1166/jbn.2015.2075
卷: 11, 期:9, 页:1568-1582
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Nanoscience & Nanotechnology ; Materials Science, Biomaterials
研究领域[WOS]: Science & Technology - Other Topics ; Materials Science
关键词[WOS]: CELL VASCULOGENIC MIMICRY ; RESISTANT LUNG-CANCER ; HEPATOCELLULAR-CARCINOMA ; TUMOR-GROWTH ; STEM-CELLS ; METASTASIS ; MECHANISM ; ANGIOGENESIS ; CONJUGATE ; APOPTOSIS
英文摘要:

Regular chemotherapy cannot eradicate invasive breast cancer cells and the residual cancer cells will form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for cancer masses prior to angiogenesis. This phenomenon is a major reason for the recurrence of invasive breast cancer after treatment. In this study, a novel type of targeted liposomes was developed by modifying a mitochondria-tropic material, D-a-tocopheryl polyethylene glycol 1000 succinate- triphenylphosphine conjugate (TPGS(1000)-TPP), to encapsulate sunitinib and vinorelbine separately and a combination of the two targeted drug liposomes was used to treat invasive breast cancer as well as VM channels. Evaluations were performed in breast cancer MCF-7 cells and highly invasive breast cancer MDA-MB-435S cells in Vitro and in mice. The results determined that the functional material (TPGS1000-TPP) and suitable size of the liposomes (90-100 nm) resulted in prolonged blood circulation, an enhanced permeability retention (EPR) effect in cancer tissue, and a mitochondrial targeting effect. Targeted drug liposonnes were internalized via cellular uptake and accumulated in the mitochondria of invasive breast cancer cells or VM channel-forming cancer cells to induce acute cytotoxic injury and apoptosis. Activated apoptotic enzymes caspase 9 and caspase 3 as well as down-regulated VM channel-forming indicators (MMP-9, EphA2, VE-Cadherin, FAK and HIF-1 alpha) contributed to significantly enhanced efficacy. Therefore, a combination of targeted sunitinib liposomes and targeted vinorelbine liposomes may provide an effective strategy for treating invasive breast cancer and prevent relapse arising from VM channels.

语种: 英语
所属项目编号: 7131009 ; 2013CB932501 ; 81172991 ; BMU20110263
项目资助者: Beijing Natural Science Foundation ; National Basic Research Program of China (973 program) ; National Science Foundation of China ; Innovation Team of Ministry of Education
WOS记录号: WOS:000359391700005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57820
Appears in Collections:北京大学药学院_期刊论文

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

Recommended Citation:
Shi, Ji-Feng,Sun, Meng-Ge,Li, Xiu-Ying,et al. A Combination of Targeted Sunitinib Liposomes and Targeted Vinorelbine Liposomes for Treating Invasive Breast Cancer[J]. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY,2015,11(9):1568-1582.
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