基于DNA纳米机器及纳米酶双重信号增强的肿瘤标志物快速检测新方法研究

Cancer is one of the most common life-threatening cause of death, the early diagnosis of cancer is an effective way to improve the cure rate. Thus, developing fast and sensitive point-of-care (POC) analysis method to realize the detection of tumor biomarker with low abundance is of significant importance. In this proposal, the basic goal is to realize the early POC diagnosis of cancer. Taking tumor biomarker as the target, we propose to develop highly sensitive lateral flow assay (LFA) based on dual signal enhancement as well as to enrich the theoretical system of relevant research field. DNA nanomachine will be designed to pre-amplify the signal, nanoenzyme (Pt-based nanomaterial, et al.) with excellent catalytic ability will be synthesized to give color signal on LFA strip. The designed DNA will be modified on the surface of nanoenzyme using nanotechnology, and the effect of DNA arrangement on the biosensor performance will be further studied. Moreover, the DNA nanomachine and nanoenzyme dual signal enhanced novel biosensor will be constructed based on the above-mentioned probe. With the help of naked eyes and smart phone APP, the fast qualitative and quantitative detection of tumor biomarker could be realized. Finally, we will expand the detection target to two kinds and more by rational design the DNA nanomachine and LFA, thus facilitating the reliable early diagnosis of tumor biomarker. The aim of this project is to provide new technology and method for early POC cancer diagnosis .

癌症是威胁人类健康的最致命疾病之一，早期诊断是提高治愈率的有效途径，因此开发快速便捷、高灵敏的低丰度肿瘤标志物检测新方法具有极为重要的意义。本项目以癌症的早期床旁诊断为目标、以肿瘤标志物为检测对象、以试纸条作为检测手段，进行快速高灵敏检测新方法的开发并丰富相关研究领域的理论体系。设计DNA纳米机器预放大待测信号，制备催化性能良好的铂基贵金属等纳米酶材料用于试纸条显色，利用纳米技术将DNA修饰在纳米酶上构建新型试纸条信标探针，研究DNA在纳米酶表面排布对传感器性能影响，进而指导创立DNA纳米机器-纳米酶双重信号增强检测新方法，结合肉眼观察和手机APP实现肿瘤标志物快速高灵敏定性及定量检测；创建单张试纸条上多种标志物同时检测新方法，提高肿瘤早期诊断的可靠性以及准确率。本项目将为癌症早期快速诊断提供新技术和新方法，为癌症早期检测走向家庭提供有效途径。

癌症是威胁人类健康的最致命疾病之一，早期诊断是提高治愈率的有效途径，因此开发快速便捷、高灵敏的低丰度肿瘤标记物检测新方法具有极为重要的意义。该项目执行期间，设计了多种新型 DNA 纳米机器信号放大方法，制备催化性能良好的纳米酶材料，构建了新型多功能生物标记探针。利用DNA纳米技术增强传统试纸条的输出信号，进一步借助手持拉曼仪提高检测的灵敏度，由于借助了多重信号输出手段，保证了肿瘤标志物检测的准确度。在此基础上，我们进一步展开了多项基于DNA纳米技术的信号转化、信号增强的策略研究，在动物病毒以及食品毒素检测方面有了广泛的应用。在本项目的支持下，共计发表论文13篇，其中影响因子大于5的论文共计12篇（Chem. Soc. Rev.(1), Anal. Chem.(3), ACS Sensors(2)等），申请专利2项，培养研究生共计4名。完成了项目提出的研究内容和既定目标。