新型嵌段DNA-纳米金荧光探针应用于循环肿瘤细胞高灵敏检测和分离的研究

As a tumor marker, circulating tumor cells (CTCs) has significant clinical value in the treatment and monitoring of cancer. The detection of CTCs from peripheral blood allows non-invasive diagnosis and real-time detection of cancer. In this project, we aim to construct a novel fluorescent nanoprobe based on the development of diblock DNA-gold nanoparticles (AuNPs) with controllable DNA density and configurations. The detection and isolation of CTCs with high sensitivity is expected to be achieved by identifying the intracellular target gene expression by this diblock nanoprobe, which has proved to possess significant advantages in DNA hybridization compared to traditional thiol DNA-AuNPs probe. By optimizing the design of DNA probes and experimental conditions, the diblock fluorescent nanoprobe is aimed to identify the target gene with high sensitivity. Therefore, the rapid detection of CTCs with improved isolation efficiency is expected to be achieved. During these processes, CTCs are supposed to remain cellular activity for further culture and research. We hope our study provide theoretical basis and experimental models for the construction of probes with high performance and supply new materials and new technologies for cancer diagnosis and pathology studies.

循环肿瘤细胞（CTCs）作为一种肿瘤标志物，在癌症的治疗和监控、肿瘤无创诊断和实时检测方面具有显著的临床应用价值。本项目基于具有可控组装密度与构型的双嵌段DNA-纳米金的制备方法，构建一种新型的嵌段DNA-纳米金荧光探针，通过识别细胞内的目标基因实现血样中CTCs的高灵敏检测与快速分选。双嵌段DNA-纳米金在分子识别和反应动力学方面具有显著的优势，相比于传统的巯基DNA-纳米金体系，具有更高的杂交效率和更快的杂交速率。本项目预期通过优化探针设计、控制多种反应条件，构建对目标基因具有高灵敏响应的纳米荧光探针，实现探针对细胞内目标基因的灵敏快速识别，希望由此提高CTCs的检测灵敏度和分离效率，缩短检测时间，并在此过程保持细胞活性，以用于人工再培养和病理研究。本项目有望为高效检测探针的构建提供理论基础和实验模型，为癌症的诊疗和病理学研究提供新材料和新技术。

循环肿瘤细胞（CTCs）作为一种肿瘤标志物，在癌症的治疗和监控、肿瘤无创诊断和实时检测方面具有显著的临床应用价值。本项目构建了系列可控组装密度与构型的双嵌段DNA-纳米金荧光检测探针，系统地研究了该探针在CTCs内过表达的mRNA目标基因检测的性能。通过基因检测结合流式细胞技术，实现了CTCs的快速成像、检测与高效分离，在此过程中可保持细胞活性，用于后续再培养及病理研究。在此基础上，发展了一系列用于肿瘤细胞成像及肿瘤标志物检测的新型荧光探针，实现了肿瘤细胞中多种目标物的高灵敏成像检测。结果表明，所构建的双嵌段DNA-纳米金探针在分子识别和反应动力学方面具有显著的优势，相比于传统的巯基DNA-纳米金体系，具有更高的杂交效率、更快的杂交速率和细胞内的响应动力学，可显著提高CTCs内目标基因的识别速率和检测灵敏度，从而有效提高CTCs的检测和分离效率。本项目的研究为高效检测探针的构建提供了理论基础和实验模型，为癌症的诊疗和病理学研究提供了新材料和新技术。