基于交联增强自组装策略构建高稳定性量子点荧光探针及其在肺癌miRNA标志物检测中的应用

项目名称： 基于交联增强自组装策略构建高稳定性量子点荧光探针及其在肺癌miRNA标志物检测中的应用

项目编号： No.51503101

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 一般工业技术

项目作者： 宇文力辉

作者单位： 南京邮电大学

项目金额： 21万元

中文摘要： 本项目面向肺癌早期诊断的重大需求，以实现基于量子点的肺癌微小核糖核酸（miRNA）标志物的高灵敏荧光检测为研究目标，针对当前量子点荧光探针稳定性不足而严重制约检测灵敏度与可靠性的问题，重点发展 “交联增强自组装”的量子点表面修饰策略，设计具有巯基链段的两亲嵌段聚合物作为表面修饰剂，利用巯基与金属离子间的配位键在量子点表面组装有序的聚合物修饰层，进而利用巯基之间的氧化交联增强表面修饰层的稳定性，突破传统策略中稳定性与荧光性能难以兼顾的局限，实现高性能量子点荧光探针的可控构建。以此为基础，制备量子点-DNA荧光探针，基于碱基互补配对原则，结合纳米磁珠的磁分离能力，发展高灵敏、高特异性的miRNA荧光检测技术。利用不同发射波长的量子点对核酸探针进行荧光编码，实现肺癌miRNA标志物的多元联合检测。本项目的实施将为量子点和其它纳米材料提供一种通用的表面修饰策略，并为肺癌的早期诊断提供技术支持。

中文关键词： 量子点；稳定性；交联增强自组装；肺癌；微小核糖核酸

英文摘要： Due to the great need for early diagnostics of lung cancer, this project is aimed to develop a novel high sensitive detection technology of miRNA biomarkers for lung cancer based on Quantum dots (QDs). In order to solve the QDs fluorescent probe’s instability problem which seriously constrains the improvement of sensitivity and liability of the detection system, we propose a ‘cross-linking enhanced self-assembly’ strategy for QD’s surface modification. This method utilizes a newly designed thiol-containing amphiphilic diblock polymer as the surface modifier. The coordinating bonds between thiol groups and metal ions on the QD’s surface are firstly used to assembly the polymer to form ordered surface modification layer. Then the excess thiol groups in the polymer shell will function as cross-linking agent via oxidation between thiol groups, which provides strong covalent bonding and significantly enhances the stability of the surface modification layer. This strategy can break through the limit of stability-luminescence contradiction derived from either traditional surface modification strategies and produces high performance QD fluorescent probes in controlled manner. Based on the high quality QDs, QD-DNA fluorescent probes can be prepared and used to construct a highly sensitive miRNA fluorescence detection platform under base-pair complementary principle combined with magnetic separation of nano-magnetic beads. QDs with different emission colors can be used to prepare fluorescence programmed bioprobes and to simultaneously detect multiple lung cancer miRNA biomarkers with high sensitivity and specificity. This project will provide a versatile surface modification strategy for both QDs and other nanomaterials, and can offer potentially useful detection technology for lung cancer diagnostics.

英文关键词： Quantum Dots;Stability;Cross-linking enhanced self-assembly;Lung cancer;miRNA