动脉粥样硬化斑块的NIRF-II/MRI双模态分子成像研究

Today’s concept of vulnerable plaque has evolved primarily from the early pioneering work uncovering the pivotal role of plaque rupture and coronary thrombosis as the major cause of acute myocardial infarction and sudden cardiac death. Early detection and acute treatment of vulnerable plaque morphology and composition remains a challenging task in cardiovascular research areas. In this project, VCAM-1, macrophages, and fibrin can be used as targets for atherosclerosis origination, development, and the late stage, respectively. On the basis of our previous research involved in the synthesis of second near-infrared window fluorescence (NIRF-II) emitting organic molecules, this project aims to synthesize a series of novel NITF-II/MRI dual-modality imaging probes through a variety of platforms such as SV40 virus-like particles (VLPs) and small-molecule NIF-II dye H1 with high specificity, deep tissue imaging capability, high spatial and temporal resolution, and high contrast. A powerful synergy will be achieved by combining MRI contrast and NIRF-II optical tracers for subsequent accurate delineation of vulnerable plaques with significant improvements in spatial resolution and imaging depth. This project will provide a simple, rapid and reliable method for imaging atherosclerosis and studying the dynamic development of atherosclerotic plaque at different stages in live ApoE（-/-）mice, and it can help for early diagnosis of atherosclerosis, plaque risk prediction, drug treatment assessment, and surgical localization.

动脉粥样硬化易损斑块所导致的斑块破裂、血栓形成和血管阻塞是引起冠心病及缺血性脑血管病发生的主要原因。如何实现对易损斑块形态和成分性质的早期诊断，并进行有效的干预是心血管研究领域亟待解决的科学问题。本项目拟以VCAM-1，巨噬细胞以及纤维帽为靶点，SV40主要衣壳蛋白VP1和小分子近红外染料H1分别作为纳米载体和平台分子，构建一系列动脉粥样硬化不同时期阶段的NIRF-II/MRI双模态探针，发挥MRI解剖成像，以及近红外II区有机小分子探针高灵敏度、高时空分辨率、强生物组织穿透能力等优势，实现ApoE（-/-）模型鼠的活体显像和动脉粥样硬化斑块动态发展跟踪研究，以期获得高动脉粥样硬化易损斑块摄取、高对比度以及高质量的NIRF-II区/MRI图像，建立活体、立体化可视化技术。本研究将为动脉粥样硬化的早期诊断、斑块危险预计、药物治疗评估、手术定位等研究打下扎实基础。

动脉粥样硬化易损斑块所导致的斑块破裂、血栓形成和血管阻塞是引起冠心病及缺血性脑血管病发生的主要原因。如何实现对易损斑块形态和成分性质的早期诊断，并进行有效的干预是心血管研究领域亟待解决的科学问题。项目负责人新开发出一系列靶向功能的NIR-II，NIR-IIa, NIR-IIb，NIR-II/PET和NIR-II/MRI探针，有效突破了现有临床荧光成像背景干扰大、成像深度浅等瓶颈，实现了血管类疾病、动脉粥样硬化和肿瘤的精准定位、成像、切除以及“可视化”靶向治疗，达到精度、深度和组织功能鉴定的有机统一。以通讯作者/共同通讯作者发表SCI论文25篇，原创性成果发表在Chem. Rev.，Nat. Commun.，Chem. Sci.，J. Med. Chem., J. Control. Release等国际一流期刊上，其中4篇入选ESI高被引；获得中国授权发明专利7项和美国授权发明专利授权1项（部分成果已转让）。本研究将为血管类疾病、动脉粥样硬化和肿瘤的早期诊断、药物治疗评估、手术定位等研究打下扎实基础。