构建检测循环肿瘤细胞抗“失巢凋亡”活性的AIE 探针

依据循环肿瘤细胞抗“失巢凋亡”的分子结构基础，构建聚集诱导发光分子探针（AIE probe），标记循环肿瘤细胞内涵体中，纳米尺度整联蛋白活化聚集体，检测以这个聚集结构为核心的，CTC 细胞生长信号平台的建立与活化。AIE探针靶向结合模拟循环肿瘤细胞的整联蛋白受体，受体介导内吞，膜胞转运探针进入内涵体。在内涵体中，单体整联蛋白活化聚集，诱导探针聚集发光。被标记的整联蛋白活化聚集体与标记粘着斑激酶分子（FAK）在荧光信号在内涵体膜上发生共定位，标志CTC生长信号平台的建立和活化。通过分析这种共定位斑点不同光谱荧光强度，分析探针荧光强度变化与信号平台活性的相关性，计算检测信号平台活化探针荧光强度阈值，建立相关分析方法系统。对CTC抗“失巢凋亡”活性变化进行可视化的定性、定位及定量分析。利用构建的探针及分析系统，进一步CTC的转移能力和恶性程度，抗肿瘤药物的治疗效果等。

Based on the molecular mechanism of the CTC (circulating tumor cell) escape anoikis, engineering molecular probe of aggregation induced luminescence (AIE) label the nanoscale aggregation of activated integrin. In endosome of CTCs, activated integrins aggregate and assemble to form aggregation with nanoscale to recruits and activates focal adhesion kinase (FAK) in cytoplasm to locate on surface of endosome. Activated p-FAK recruits other protein to build a platform of growth signal in CTC to escape anoikis and persistently survival. The AIE probes target integrin receptor on simulation of CTC, and is transported into endosome by receptor mediated endocytosis and cellular membrane transportation system. Because the activated integrins aggregate and assemble, the AIE probes are induced luminous. The p-FAKs on endosome are labeled and to confirm building and activating of platform of growth signal by the colocalization of the probe and p-FAKs in endosome. Analysis and calculation of varied fluorescent intensity of the AIE probes in endosome which are labeled by p-FAKs ascertains a threshold value of luminescence. A standard of builded growth signals platform in endosome is suggested. Using the analysis system, visual positioning, qualitative and quantitative analysis varied activation of CTC to resist anoikis, further evaluate the metastasis and malignant degree of these CTCs. The therapeutic effect of antitumor drug can is evaluated by these, also.