基于特异性识别多肽的循环肿瘤细胞检测新方法研究

项目名称： 基于特异性识别多肽的循环肿瘤细胞检测新方法研究

项目编号： No.21273051

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 杨延莲

作者单位： 国家纳米科学中心

项目金额： 81万元

中文摘要： 侵袭与转移是恶性肿瘤最显著的特征之一，而肿瘤细胞自行脱落并进入外周血中，形成循环肿瘤细胞（CTC），是导致肿瘤转移、复发和影响疾病预后的重要因素。在外周血中检测到肿瘤细胞预示着有可能发生肿瘤转移，然而CTC在血液中浓度极低，所以发展高效的富集和检测技术对于CTC的检测具有重要意义。本项目将根据CTC表面蛋白质分子的序列和结构，设计、合成和筛选De Novo多肽对CTC表面蛋白进行特异性识别，研究多肽与靶蛋白结合的亲和力和特异性。并针对多个靶点或者相同靶蛋白的不同表位，将特异性识别多肽进行柔性链的功能化并组装成纳米结构，或者将不同的特异性识别多肽混合修饰在纳米颗粒表面，并将此功能化多肽修饰纳米结构组装于图案化微结构的表面形成多尺度表面结构，提高CTC与表面碰撞时的有效接触面积和相互作用位点，从而提高CTC富集和检测的灵敏度和特异性，为肿瘤转移预警和疾病预后提供基础。

中文关键词： 多肽；循环肿瘤细胞；纳米材料；液体活检；捕获

英文摘要： Metastasis is the notorious characteristics of the malignant tumors. The tumor cells that have detached from a primary tumor and circulate in the bloodstream is called circulating tumor cells (CTC), which play critical role in metastasis, and spread of carcinomas. Since the concentration of CTC is extremely low in the blood, the highly efficient enrichment and detection of CTC in peripheral blood is very important in prognosis and therapy of tumors. In this project, we will design, synthesize and screen the De novo designed peptides according to specific proteins on CTC surfaces. The specific recognition peptides will be applied rather than antibodies in enrichment and detection of CTCs. The interaction mechanism between the specific recognition peptides and the target proteins will be studied concerning the binding affinity and specificity. Taking into account the different target proteins or different epitopes on one target, different specific recognition peptides will be functionalized into peptide modified nanostructures, either by self-assembly via linking onto flexible polymer chains, or by functionalization of nanoparticles by different peptides. Those peptide modified nanostructures bearing different targets will be immobilized onto the patterned surface for construction of multiscale surface structures,

英文关键词： peptide；circulating tumor cells；nanomaterials；liquid biopsy；capture