乳腺癌干细胞(BCSC)是乳腺癌发生、侵袭和复发的主要因素，目前单一靶标的肿瘤靶向治疗对多基因变异的乳腺癌疗效不佳，针对BCSC的多靶向治疗将是乳腺癌治疗的一个新方向。因此，对BCSC进行活体多靶向分子成像具有重要意义。本课题组前期将顺磁性钆(Gd3+)偶联不同粒径的非镉量子点(QDs)成功制备了不同波长的MR-荧光双模态纳米颗粒(pQDs)，并在成功分离BCSC和构建乳腺癌动物模型基础上，拟采用CD44和ESA单克隆抗体分别标记pQDs，构建两种敏感性高、靶向性强的双模态分子探针(pQD700-CD44mAb和pQD800-ESAmAb)。借助高场MR和三维定量荧光成像仪，对BCSC进行活体成像并对不同靶标进行可视化区分，将获得的乳腺癌及前哨淋巴结中BCSC含量、分布等定量信息与电镜、免疫组化进行对照印证。本项目通过研究BCSC活体多靶向成像及定量分析，旨在为乳腺癌多靶向诊治提供新策略。

Breast cancer stem cells (BCSCs) are the chief culprit in development,invasion,and recurrence of breast cancers. The efficacy of single targeted therapy for breast cancer is poor due to multi-genetic variation,so targeted therapy for the BCSC based on multiple targets will be a new trend for breast cancer treatment. Therefore,in vivo molecular imaging based on multiple targets for the BCSCs is significant in clinic. In our earlier experiment,paramagnetic gadolinium (Gd3+) coupling of different size of the non-cadmium quantum dots (QDs) were successfully prepared for producing bi-mode nanoparticles (pQDs) of MR-fluorescence imaging,yielding different wavelengths due to the different diameters of QDs such as QD700 and QD800. BCSCs and models of BCSC-bearing mice were respectively and successfully isolated and established. On the basis of a new conjugated dual-mode nanoparticle (pQDs),the monoclonal antibodies of CD44 and ESA are respectively labeled with pQD700 and pQD800 in order to build a kind of bi-targeted and bi -mode molecular probe (pQD700-CD44mAb and pQD800-ESAmAb) with high sensitivity and strong targeting. With three-dimensional quantitative in vivo fluorescence imager and high-field MR scanner,BCSCs will be imaging and the different targets will be visually distinguished in vivo via dual-targeted probe. Thereby,the information of BCSCs in tumors and sentinel nodes including position,content,distribution and other results can be obtained and compared with the results of electron microscopy and immunohistochemistry. This project,through exploring BCSCs with multi-targeted imaging and quantitative analysis,aims at providing a new strategy for targeted diagnosis and therapy of breast cancer.