基于靶向多肽探针的循环肿瘤细胞高选择性分析探索

项目名称： 基于靶向多肽探针的循环肿瘤细胞高选择性分析探索

项目编号： No.21475140

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 黄嫣嫣

作者单位： 中国科学院化学研究所

项目金额： 90万元

中文摘要： 针对循环肿瘤细胞（CTCs）的分子特征，发展高选择性、高灵敏度的分析方法，可望为肿瘤转移的早期预警和个性化治疗提供新的手段。CTCs异常低的含量、缺乏特征标志物和动态变化的特点是其准确识别检测的关键难题。本项目拟针对CTCs的肿瘤特性和转移活性，以新型肿瘤标志蛋白LAPTM4B为目标，以其促进肿瘤转移相关的结构域为靶点，发展位置扫描的组合化学反义肽库构建新方法；建立多肽亲和筛选新体系，筛选出高亲和力的反义肽；以LAPTM4B蛋白靶向多肽和细胞凋亡识别多肽为元件，构建双靶向识别、荧光响应的“开/关”型多肽纳米探针，开展肿瘤活细胞的成像分析研究；探索基于识别信号响应的CTCs高选择性、高灵敏度分析检测新方法。

中文关键词： 多肽；肿瘤标志物；亲和筛选；组合肽库；循环肿瘤细胞

英文摘要： Highly selective and sensitive methods for the analysis of characteristic molecular events in circulating tumor cells (CTCs) are promising for the early diagnosis, metastasis prediction and therapeutic outcome assessment of cancer. However, detection and characterization of CTCs have been challenging owing to their extremely low content, dynamic nature and lacking of biomarkers. Herein, according to the cancerous and metastatic nature of CTCs, a novel strategy for the design and screening of peptide probes towards a new broad-spectrum biomarker LAPTM4B protein is proposed for CTCs analysis. Based on the degeneracy of antisense peptides, position-scanning peptide libraries are designed by choosing a metastasis-related domain as the target. A novel screening system is developed by using binding-activated fluorescence assay to obtain an optimal antisense peptide. With the high specificity and affinity, the screened peptide will be further applied in targetable bioimaging of tumor cell and real-time tracking of LAPTM4B protein. Taking advantage of the LAPTM4B-targeting peptide and the apoptosis-responsive caspase-3 substrate peptide, a multi-functional activatable nanoprobe is constructed. According to the on-off signals, highly selective and sensitive detection of live CTCs in the blood stream can be realized. This work can provide a foundation for the development of a clinically available method for CTCs analysis and important information for understanding the molecular mechanism of tumor metastasis.

英文关键词： peptide;cancer biomarker;affinity screening;combinitorial peptide library;circulating tumor cells