新型hERG钾通道探针及其在GBM肿瘤成像与治疗中的应用研究

多形性神经胶质母细胞瘤属于IV级神经胶质瘤，恶性程度高，确诊后生存期仅为15-17个月，因此临床急需全新有效的诊断、预后及治疗策略等。近年来，越来越多的研究显示hERG钾通道在GBM肿瘤细胞中表达上调，而在正常星形胶质细胞及低度恶性脑胶质瘤细胞中无表达，同时发现hERG钾通道与患者的低生存率相关，因此hERG钾通道可作为GBM肿瘤检测及其预后的生物标志物。. 本项目将在前期工作基础上，设计构建具有较低成像背景及较高成像深度的近红外余辉发光hERG钾通道探针，并对其生物学活性进行研究，以期发现可用于hERG钾通道在体成像的探针分子，并进一步探索hERG钾通道成像在GBM肿瘤检测、术中导航及治疗中的应用。通过本项目研究，将为GBM肿瘤提供新颖的诊断、预后及治疗策略，同时为hERG钾通道的在体研究提供强有力的技术手段。

Glioblastoma (GBM), a high grade of gliomas（IV）, is the most common and magligant primary brain cancer. Due to its high aggressiveness feature, the prognosis for patients suffering from GBM is very poor and the median survival time is 15-17 months. Therefore, there remains an urgent clinical need for novel diagnosis, prognosis and therapy strategies. Recent years, many research revealed that the expression of hERG channel was obviously upregulated in GBM cancer cell, while absent in normal astrocyte and low-grade gliomas. Moreover, GBM patients with high hERG channel expression showed worse survival. Therefore, hERG channel is a potential biomarker for Glioblastoma and the survival of patients. . In this project, on the basis of previous work, we will design and synthesize a series of near-infrared afterglow luminescence probes for hERG channel. Because of lack of real-time excitation, it can eliminate tissue autofluorescence and has a lower background signal. After a series of biological evaluation, we hope to discover several probes that can be used in hERG channel imaging in vivo, and then we will further explore their application in GBM imaging, surgical navigation and therapy. The work in this project may provide a novel diagnosis, prognosis and therapy strategy for glioblastoma, and also provide a powerful tool for hERG potassium channel in vivo research.