适配子修饰的PLGA纳米基底特异性捕获循环肿瘤细胞和单细胞分析的研究

项目名称： 适配子修饰的PLGA纳米基底特异性捕获循环肿瘤细胞和单细胞分析的研究

项目编号： No.81472748

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 沈庆林

作者单位： 华中科技大学

项目金额： 72万元

中文摘要： 循环肿瘤细胞（CTC）可以被看作肿瘤的液态标本，为原发瘤和转移瘤提供了便捷和无创的检测途径。近十年来已开发了原理各异的CTC检测技术，但CTC数量极少, 检测和分析CTC仍受到技术上的挑战。我们前期进行了用Cell-SELEX筛选的适配子修饰硅纳米芯片特异性捕获CTC和用核酸酶特异性释放CTC的研究，经过两轮捕获-释放后可获得高纯度和高活性的CTCs。本研究将进一步探讨用适配子修饰PLGA纳米芯片来特异性捕获肺癌病人外周血CTCs，然后运用激光显微切割技术把捕获的CTCs单个切割下来。对单个CTC进行基因点突变检测和外显子组测序，结果将为无创的肿瘤诊断、疗效评价、预后判断以及个体化治疗提供及时可靠的依据；也有助于我们更好地了解肿瘤转移的生物学机制。

中文关键词： 循环肿瘤细胞；适配子；纳米基底；单细胞分析

英文摘要： CTCs can be regarded as the 'liquid' biopsy of the tumor, thus providing convenient and noninvasive access to primary and metastatic tumor cells. Over the past decade, a diversity of technologies capable of detecting CTCs have been developed based on different operation mechanisms.However, detection and characterization of CTCs has been technically challenging due to the extremely low abundance of CTCs in the peripheral blood. Previously,we performed specific capture of CTCs in patients blood samples using aptamer which screened by cell-SELEX process modified nanosubstrates and carried out specific release of immobilized CTCs by treatment nuclease.We recovered high purity and viability CTCs from the two rounds of capture/release processes. In this project, we will further explore specific capture of CTCs in lung cancer patients blood using aptamer modified PLGA-nanosubstrates,and cut out single CTC using laser microdissection(LMD).We perform single CTC gene point mutation detection and exome sequencing,and analyses of CTCs could provide timely and reliable evidences on non-invasive cancer diagnosis, prognosis,response to therapy, prediction drug sensitivity and guidance individualized therapy; and it also helps us better understand the biological mechanisms of tumor metastasis.

英文关键词： Circulating tumor cells;aptamer;nanosubstrates;single cell analysis