基于亲和多肽的新型荧光纳米传感器构建及其在肿瘤干细胞标志物检测中的应用

项目名称： 基于亲和多肽的新型荧光纳米传感器构建及其在肿瘤干细胞标志物检测中的应用

项目编号： No.21505042

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 黄伟涛

作者单位： 湖南师范大学

项目金额： 21万元

中文摘要： 肿瘤干细胞是导致肿瘤发生、转移、复发及放化疗耐药的根源，快速、灵敏、准确检测其标志物，有助于肿瘤早期诊断和疗效评估。研究发现，特定氨基酸序列的亲和多肽可特异性识别肿瘤干细胞标志物。本项目旨在基于CD44、CD133、巢蛋白特异性识别多肽，结合具有独特光学、易与生物分子相互作用、功能化等特性的纳米材料，构建新型荧光纳米传感器。借助化学合成、修饰、偶联/纳米标记等手段，设计并制备功能化(单功能、多功能融合、DNA杂交)亲和多肽探针，探寻其合理设计的一般性原则；结合分子自组装、纳米技术及酶信号放大技术，实现亲和多肽在纳米猝灭剂平台上的传感识别、信号转换与放大。阐明新型多肽荧光纳米传感器构建的基本原则与规律，建立高灵敏度、高选择性检测肿瘤干细胞标志物的新技术和新方法。这不仅为开发新型多肽传感器提供理论和实验基础，更为肿瘤的早期诊断及疗效评估提供科学依据。

中文关键词： 亲和多肽；功能纳米材料；纳米生物技术；肿瘤干细胞标志物；肿瘤早期诊断

英文摘要： Cancer stem cells (CSCs) are thought to be responsible for growth and dissemination of many malignant tumors and for relapse after therapy. Therefore, the rapid, sensitive and accurate detection of CSC markers, can be helpful for early diagnosis and efficacy assessments of tumor. Studies have shown that, affinity peptides with specific amino acid sequences can specifically recognize CSC markers. The proposed research aims to base on the selected affinity peptide sequences with specific binding for CSC markers, including CD44, CD133 and Nestin, combine with nanomaterials which have unique optical and functional properties, and are easy to interact with biomolecules, to construct novel fluorescent nanosensors.. By utilizing chemical synthesis, modification, chemical coupling, or nano-labeling, we design and prepare functional (singe functional, multi-functional fused, DNA hybrid) affinity peptide probes, and discover the general principles for rational designing of peptide probes. Then combined with molecular self-assembly, nanotechnology, and enzymatic amplification technology, we implement the processes of sensing, signal transduction and amplification of the designed probes on nanoquencher platforms, illustrate the basic principles for fabricating the peptide-based novel fluorescent nanosensors, and establish novel methods and techniques for highly sensitive and highly selective sensing CSC markers based on different strategies. The research not only provides theoretical and experimental foundations for developing novel peptide-based analytical technology, but also gives a scientific basis for early diagnosis and efficacy assessments of tumor.

英文关键词： Affinity peptides;Functional nanomaterials;Nanobiotechnology;Cancer stem cell markers;Early diagnosis of tumor