肿瘤微环境响应性探针用于脑胶质瘤的近红外II区成像研究

The vexing difficulty in delineating brain tumor margins represents a major obstacle toward better outcome of brain tumor patients. Current imaging methods are often limited by inadequate sensitivity, specificity, and spatial resolution. Here, we will develop a tumor microenvironment-responsive probes for in vivo second near-infrared window (NIR-II) imaging of glioma. Fluorescent imaging of biological systems in NIR-II is a new imaging modality that can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Designed probe have an enhanced ability to respond to tumor microenvironment (such as pH or hypoxia response ) and cross the blood brain barrier (BBB). So it can accurately help delineate the margins of brain tumors in living mice both pre- and intra-operatively and gave a five times higher tumor/normal tissue tissue ratio than traditional NIR-I imaging, allowing accurate image-guided tumour-removal surgery.

本课题针对脑胶质瘤边界不清，一般光学影像难以对脑胶质瘤进行清晰成像，普通探针难以跨越脑血屏障的难题，以前期的激活型荧光探针、pH荧光探针、还原响应荧光探针的研究工作和新近搭建的近红外II区成像系统为基础，利用近红外II区成像更强的组织穿透优势，设计新型的具有肿瘤微环境响应（如pH或乏氧响应）和血脑屏障穿越能力的近红外II区分子探针以实现对脑胶质瘤的近红外II区成像和肿瘤的边界确认。本项目突出解决近红外II区分子探针高效跨越血脑屏障、实现近红外II区的脑胶质瘤成像及其影像学边界确认等关键科学问题，对于推动近红外II区成像引导的手术导航与精准治疗具有积极意义。

本项目从2017年1月开始，到2020年12月结束，为期四年。我们按原定计划开展了研究，建立了具有肿瘤微环境响应性近红外II区分子探针。实现探针的近红外II区成像，解决近红外II区分子探针高效跨越血脑屏障、实现近红外II区的脑胶质瘤成像及肿瘤影像学边界确认。并取得了预期的研究成果，已全面地完成了预期的考核指标。迄今为止，本项目在国内外核心期刊发表研究论文25篇，SCI收录24篇；会议4篇；申请专利7项；获得高交会优秀产品奖；国际和国内学术会议专题报告或讲座5次。在本项目研究成果的基础上，本课题组多人获得国家自然基金、博后基金、广东省自然基金和深圳市科创委的支持。研究中形成一支稳定的、多学科交叉的、由以青年为主的科研人员梯队。