核酸适体功能化微流控芯片用于外泌体高效富集与可控释放及在肿瘤检测与转移机制的研究

Nasopharyngeal carcinoma metastasis is the main cause of invalid treatment. The early warning of metastasis can effectively improve the survival rate of patients. Exosomes, which deliver information between cells, are closely related with cancer pathogenesis, invasion and metastasis. Evaluation of cancer specific exosomes has become a new tool for cancer diagnosis. However, the ultrasensitive capture and controlled release of tumor specific exosomes from blood is the main technical challenge in the analysis of exosomes. Based on previous aptamer screening experiments and development of the microfluidic technology, aptamers against LMP1, the nasopharyngeal carcinoma (NPC) marker, will be generated in this project. Combined with highly-programmed and automated microfluidic chip, an aptamer-based microfluidic chip will be designed and fabricated for selectively capturing LMP1 positive exosomes from patients’ blood. Benefiting from the advantages of aptamers, exosomes can be released from the chip without any damage. This project will build up a new platform to evaluate the early metastasis of NPC using numbers of exosomes in patients’ blood. This research team has a strong background in aptamers selection, microfluidic chips application and clinical research, which lays a solid foundation to operate the proposed project.

鼻咽癌转移是导致治疗失败的主要原因，加强鼻咽癌转移的早期预警可有效提高患者的生存率。研究表明肿瘤外泌体与肿瘤的发生及转移密切相关，是新型肿瘤标志物的研究热点。而如何简便高效获取且无损可控释放特异性的肿瘤外泌体是目前外泌体分析检测及研究肿瘤转移机制的一大瓶颈。前期工作已筛选多条特异性识别肿瘤蛋白的核酸适体，并建立了核酸适体功能化微流控技术，本项目拟在此基础上，通过指数富集的配基系统进化技术筛选鼻咽癌标志物LMP1核酸适体；利用核酸适体作为探针，进行肿瘤外泌体的特异性捕获和无损可控释放；采用功能化微流控芯片体系，实现高通量、全自动、低成本的特异性外泌体高效富集纯化；最终实现对鼻咽癌患者LMP1阳性肿瘤外泌体高灵敏、高选择的快速检测、高效富集与无损释放。项目的成功实施将建立对鼻咽癌转移扩散的预测、早期诊断及疗效监测的新方法，揭示LMP1阳性外泌体介导鼻咽癌转移机制，提高患者生存率，改善生存质量。

鼻咽癌转移是导致治疗失败的主要原因，加强鼻咽癌转移的早期预警可有效提高患者的生存率。研究表明肿瘤外泌体与肿瘤的发生及转移密切相关，是新型肿瘤标志物的研究热点。而如何简便高效获取且无损可控释放特异性的肿瘤外泌体是目前外泌体分析检测及研究肿瘤转移机制的一大瓶颈。前期工作已筛选多条特异性识别肿瘤蛋白的核酸适体，并建立了核酸适体功能化微流控技术，本项目拟在此基础上，通过指数富集的配基系统进化技术筛选鼻咽癌标志物LMP1核酸适体；利用核酸适体作为探针，进行肿瘤外泌体的特异性捕获和无损可控释放；采用功能化微流控芯片体系，实现高通量、全自动、低成本的特异性外泌体高效富集纯化；最终实现对鼻咽癌患者LMP1阳性肿瘤外泌体高灵敏、高选择的快速检测、高效富集与无损释放。项目的成功实施将建立对鼻咽癌转移扩散的预测、早期诊断及疗效监测的新方法，揭示LMP1阳性外泌体介导鼻咽癌转移机制，提高患者生存率，改善生存质量。