T-VISA-miR-200纳米系统靶向治疗三阴乳腺癌及其作用机制的研究

三阴乳腺癌（Triple Negative Breast Cancer, TNBC）是一种预后极差的特殊类型乳腺癌，约占所有乳腺癌的20%，因其ER、PR及HER2均为阴性，内分泌治疗和抗HER2靶向治疗均无效。近年研究发现miR-200可明显抑制TNBC增殖、转移，并可同时降低其干细胞活性，因此我们认为miR-200具备开发成为TNBC靶向药物的潜质。本课题前期在VISA基因扩增系统（美国专利号：US7723104B2）及脂质体纳米颗粒的基础上，建立了三阴乳腺癌特异性T-VISA 纳米靶向载体（中国专利申请号: 2011103300441.X），现欲构建T-VISA-miR-200纳米系统，将miR-200高效特异的表达于TNBC中，评价其治疗的安全性及有效性。探索miR-200作用于TNBC的分子机制，利用GO、Pathway等软件绘制信号通路网络，为靶向治疗TNBC奠定基础。

Triple negative breast cancer (TNBC) is the most aggressive subgroup with the highest metastasis rate and poorest survival, accounting for about 20% of all cases of breast cancer. Owing to the absence of estrogen-receptor (ER), progesterone-receptor (PR) and human epidermal growth factor receptor type 2 (HER2), the patients with TNBC could benefit neither from endocrine therapy nor from HER-2-targeted therapy. With numerous studies of microRNAs profiles in recent years, miR-200 is identified to be down-regulated in TNBC. The over-expression of miR-200 could inhibit the proliferation, metastasis and chemotherapy resistance in TNBC significantly, through targeting multiple oncogenes. Therefore, we anticipate the potential of miR-200 for being developed as a targeted drug of TNBC. Based on VISA Integrated Systemic Amplifier (u.s. patent no. US 7723104 B2) and nanoparticle XM001 technology, we constructed the TNBC specific T (hTERT)-VISA nanoparticle vector system. Now we want to synthetize T-VISA-miR-200 nanoparticle targeted system, which initiates the over-expression of miR-200 in TNBC efficiently and specifically. Then the safety and effectiveness of T-VISA-miR-200 nanoparticle targeted system will be evaluated. Furthermore, the mechanism of miR-200 regulating TNBC will be explored by using analysis software such as GO and Pathway, and there will be more new molecular targets unrevealed, which lays a theoretical foundation for targeted therapy of TNBC.