靶向细菌粘附素FimH的近红外分子探针的构建及其细菌诊疗一体化研究

细菌感染性疾病严重威胁人类生命健康，且日趋严峻，现有诊疗手段难以满足临床需求。一方面由于病原菌的多样性导致临床诊断困难，而传统抗生素耐受、多重耐药、新型抗菌药物缺乏等造成治疗日俱挑战。本项目旨在创制诊疗细菌感染的新型分子探针：通过生物正交反应偶联具有AIE和光敏剂效应的信号组件四芳基咪唑（TPI）、靶向细菌粘附素FimH的分子和光热剂，巧妙构建新型诊疗一体化分子探针。该分子探针在体内通过血液循环靶向聚集于感染部位，实现细菌的荧光成像和原位快速诊断；局域近红外光照治疗以激活TPI组件产生活性氧杀伤细菌以实现光动治疗；同时ROS响应释放光热分子以同时实现光热治疗和有利于深部组织的光声成像。本项目是在我们良好的前期工作基础上，利用多模态成像技术的优势互补，实现对细菌的近红外光响应下的多模态成像（荧光、光声）和多模式（PDT和PTT）协同治疗，有望实现细菌感染的诊疗一体化，为临床抗菌提供新方案。

Bacterial infectious diseases are a major threat to human life and health. The existing diagnosis and treatment methods are difficult to meet clinical needs. On the one hand, clinical diagnosis is difficult due to the diversity of pathogenic bacteria, while traditional antibiotic resistance, multi-drug resistance, and lack of new antibacterial drugs result in increasing challenges in bacterial treatment. This project aims to create a novel probe for the diagnosis and therapy of bacterial infections: the signal component tetraarylimidazole （TPI） with AIE and photosensitizer properties, is connected to a new type of photothermal agent molecule through a reactive oxygen-sensitive bond, and the other end is coupled to FimH-binding ligand for bacterial targeting. This probe can accumulate at the sites of infection through the blood circulation for fluorescence imaging and rapid in-situ diagnosis. Local near-infrared irradiation activates TPI components to generate reactive oxygen species and kill bacteria to achieve photodynamic therapy; Meanwhile ROS responsive release of photothermal agents, leading to photothermal therapy and photoacoustic imaging. This project is based on our good preliminary work, we utilize NIR light-responsive multi-modal imaging (fluorescence, photoacoustic) and multi-phototherapy (PDT and PTT) strategy for the diagnosis and therapy of bacterial infections, providing novel solutions for clinical antibacterial treatment.