乳腺癌干细胞(BCSCs)是导致乳腺癌耐药、复发和转移的根源之一。最近研究表明，microRNAs(miRs) 参与了BCSCs的分化、自我更新等生物学特性的调控。本项目前期研究发现：1、miR-708在乳腺癌细胞和乳腺癌干细胞中低表达，CD44是其直接靶基因；2、miR-708过表达可降低肿瘤细胞中CD44+/CD24-细胞群的比率，有效抑制乳腺癌干细胞成球；3、基于肿瘤特异性启动子的TV载体系统能高效靶向乳腺癌及其干细胞（Xie et al.MCT.2012）；4、脂质体纳米颗粒XM001具有靶向输送TV-miRs的能力(Xie et al.MT.2012)。因此，申请者拟在前期工作基础上，构建高效、高特异性的TV-miR-708纳米治疗系统，研究其在乳腺癌干细胞中的疗效、靶向性和安全性，并进一步探讨TV-miR-708在乳腺癌干细胞中的作用机制，为乳腺癌提供新的、更有效的治疗策略。

Breast cancer stem cells (CSCs) is the resource of breast tumor recurrence, metastasis and drug-resistance. Recently, it was reported that microRNAs (miRs) regulated the differentiation, self-renewal of BCSCs. In my research projects, we demostrated that miR-708 expression was attenuated widely in human breast tumor specimens and stem cells. CD44 is a derect target of miR-708. Restoration of miR-708 expression in BCSCs decreased CD44+/CD24- population and effectively suppressed the mamosphere of BCSCs. Our TV vector system based cancer-specific promoter can target breast tumor and BCSCs with no cytotoxic effects in normal cells. Liposome nanoparticles XM001 guaranteed the TV-miRs plasmid localized in the targeted tumor cells. Taken together, the purpose of our study is to engineer TV-miR-708 nanoparticles treatment system, and then analyzed its killing effects and targeted expression in vitro and in vivo, as well as the side effects. Moreover, the action mechanism of TV-miR-708 in BCSCs will be explored in depth. Therefore, a novel and valid treatment strategy will be avalable for breast cancer.