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The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles
Zhang, Yang; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang
关键词Breast cancer Paclitaxel Polymeric micelles Somatostatin receptors Cancer stem cells Salinomycin
刊名BIOMATERIALS
2012
DOI10.1016/j.biomaterials.2011.09.072
33期:2页:679-691
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National Science Foundation ; National Basic Research Program of China ; National Science Foundation ; National Basic Research Program of China
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]IN-VITRO ; TUMOR VASCULATURE ; DRUG-DELIVERY ; ANTICANCER EFFICACY ; COPOLYMER MICELLES ; POLYMERIC MICELLE ; VIVO ; RESISTANCE ; GROWTH ; CHEMOTHERAPY
英文摘要

Tumor stem cells have emerged as the new targets for anti-cancer therapy, besides tumor cells themselves. To eradicate both breast cancer cells and breast cancer stem cells which can not be eliminated by the conventional chemotherapy, octreotide (Oct)-modified paclitaxel (PTX)-loaded PEG-b-PCL polymeric micelles (Oct-M-PTX) and salinomycin (SAL)-loaded PEG-b-PCL polymeric micelles (M-SAL) were developed and investigated in combination. In this study, Oct that targets somatostatin receptors (SSTR) overexpressed in tumors including breast cancer, was coupled to the PEG end of PEG-b-PCL, and all the micelles were prepared using thin film hydration method. Results showed that the particle size of all the micelles was approximately 25-30 nm, and the encapsulation efficiency was >90%. Quantitative and qualitative analysis demonstrated that Oct facilitates the uptake of micelles in SSTR overexpressed breast cancer MCF-7 cells while free Oct inhibited cellular uptake of Oct-modified micelles, revealing the mechanism of receptor-mediated endocytosis. Breast cancer stem cells (side population cells, SP cells) were sorted from MCF-7 cells and identified with the CD44+/CD24- phenotype. M-SAL was capable of decreasing the proportion of SP cells, and its suppression was more potent in SP cells than that in cancer cells. As compared to PTX-loaded micelles (M-PTX), the inhibition of Oct-M-PTX against MCF-7 cells was stronger while such effect significantly increased when applying Oct-M-PTX in combination with M-SAL In the MCF-7 xenografts, the combination therapy with Oct-M-PTX plus M-SAL produced the strongest antitumor efficacy, in accord with the combination treatment in vitro. Compared with free SAL, M-SAL was found to be more effective in suppressing breast cancer stem cells in vivo. Thus, this combination therapy may provide a strategy to improve treatment of breast cancers for eradication of breast cancer cells together with breast cancer stern cells. (C) 2011 Elsevier Ltd. All rights reserved.

语种英语
所属项目编号81130059 ; 2009CB930300
资助者National Science Foundation ; National Basic Research Program of China ; National Science Foundation ; National Basic Research Program of China
WOS记录号WOS:000297879200031
引用统计
被引频次:92[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/400002259/60634
专题北京大学药学院
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Yang,Zhang, Hua,Wang, Xueqing,et al. The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles[J]. BIOMATERIALS,2012,33(2):679-691.
APA Zhang, Yang,Zhang, Hua,Wang, Xueqing,Wang, Jiancheng,Zhang, Xuan,&Zhang, Qiang.(2012).The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles.BIOMATERIALS,33(2),679-691.
MLA Zhang, Yang,et al."The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles".BIOMATERIALS 33.2(2012):679-691.
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