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学科主题: 药学
题名:
Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic octapeptide modified liposomes for targeting integrin alpha 3 in triple-negative breast cancer
作者: Dai, Wenbing1; Yang, Fang1; Ma, Ling1; Fan, Yuchen1; He, Bing1; He, Qihua2; Wang, Xueqing1; Zhang, Hua2; Zhang, Qiang1
关键词: Triple-negative breast cancer ; Liposomal doxorubicin ; Targeting delivery ; Rapamycin ; Combined therapy
刊名: BIOMATERIALS
发表日期: 2014-07-01
DOI: 10.1016/j.biomaterials.2014.03.036
卷: 35, 期:20, 页:5347-5358
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]: INDUCIBLE FACTOR-I ; DRUG-COMBINATION ; TUMOR-CELLS ; EXPRESSION ; MDA-MB-231 ; RECEPTORS ; CARCINOMA ; APOPTOSIS ; THERAPY ; GROWTH
英文摘要:

A novel therapeutic strategy combining mTOR inhibitor rapamycin (RAPA) and doxorubicin (DOX)-loaded cyclic octapeptide liposomes for targeting integrin alpha 3 was expected to combat the triple-negative breast cancer (TNBC). RAPA was loaded into PEG-PCL polymer micelles (M-RAPA) to realize solubilization. Flow cytometry analysis and laser confocal microscopy were used to evaluate the in vitro cellular uptake. The in vivo tumor targeting and bio-distribution were investigated by living fluorescence imaging. As the results, LXY modification significantly enhanced the cellular uptake of liposomal DOX in integrin alpha 3 overexpressed TNBC cells (MDA-MB-231) in vitro and accordingly improved the tumor accumulation of liposomes in vivo. When used alone or in combination with IXY-LS-DOX, M-RAPA could greatly inhibit the expression of HIF-1 alpha protein, which is always highly expressed in malignant cancers and involved in tumor angiogenesis, proliferation, therapeutic resistance and poor prognosis. Meanwhile, the improved efficacy of combined targeted therapy with LXY-LS-DOX and M-RAPA was demonstrated by the in vitro cytotoxicity against model TNBC cells and in vivo anti-tumor activity against mouse bearing TNBC model. These results suggested that the targeted combinational therapy based on LXY-LS-DOX and M-RAPA systems may provide a rational strategy to improve therapeutic outcomes of TNBC. (c) 2014 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81130059 ; 2009CB930300
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000336471300008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62331
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, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Dai, Wenbing,Yang, Fang,Ma, Ling,et al. Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic octapeptide modified liposomes for targeting integrin alpha 3 in triple-negative breast cancer[J]. BIOMATERIALS,2014,35(20):5347-5358.
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