基于聚集诱导发光的深红/近红外荧光探针的合成及其在细菌成像和光动力杀菌中的应用研究

Bacterial infections pose a serious threat to human health. Photodynamic therapy is an effective medical treatment to solve the problem of bacterial resistance, which has the advantages of low toxicity, less invasive and less side effects. Comparing with the traditional organic small molecule photosensitizers, the appearance of aggregation induced emission luminogens not only overcomes the shortage of aggregation induced quenching in water medium, but also has high fluorescence quantum yield and effective generation ability of reactive oxygen species . However, the development of facile routes to far red/near-infrared aggregation induced emission probes with broad-spectrum imaging and photodynamic killing of bacterial remains an urgently needed and challenging task facing scientists.. In this project, a series of fluorescent probes with far red/ near-infrared emission will be efficiently prepared by simple protocol via a few step reactions. The aggregation induced emission properties and reactive oxygen speicies generation efficiency will be tested. In addition, the imaging ability of gram-positive and gram-negative bacteria in vitro and the photodynamic killing effect of bacteria in vivo will be systematically evaluated to reveal the relationship between the molecular structure, imaging ability and photodynamic killing effect of bacterial.. The implementation of this project will provide theoretical guidance for the development of novel theranostic agents with long wavelength for clinical research and application.

细菌感染已经对人类健康构成严重威胁。光动力疗法具有毒性低、侵入性小、副作用少等优点，是解决细菌耐药问题的一种非常有效的治疗方法。与传统的有机小分子光敏剂相比，聚集诱导发光材料的出现不仅克服了其在水介质中存在的聚集诱导淬灭的缺点，而且具有高荧光量子产率和有效的活性氧生成能力。但是开发能够简单合成的、具有广谱细菌成像和光动力杀菌功能的深红/近红外聚集诱导发光探针分子依然是一个极大的挑战。. 本项目拟通过简单的合成方法，高效地制备一系列具有深红/近红外发射的荧光探针分子，测试其聚集诱导发光性质及活性氧产生效率，并系统考察它们对革兰阳性菌和阴性菌的成像以及活体层面的光动力杀菌效果，从而揭示分子结构与细菌成像能力和光动力杀菌效果之间的构效关系。. 本项目的执行将为更多用于临床研究和应用的新型长波长细菌感染性疾病诊疗一体化材料的开发提供理论指导。

多重耐药细菌对人类健康构成严重威胁。开发用于治疗耐多药细菌引起的感染的替代疗法和诊疗试剂仍然是一个全球性挑战。在此项目中，我们开发了一系列近红外阴离子-π+聚集诱导发光光敏剂（AIE-PSs）并成功将其用于广谱多重耐药细菌的根除。由于强大的分子内电荷转移和增强的系间窜越能力，这些富电子的阴离子-π+ 聚集诱导发光光敏剂显示出增强的I型活性氧生成能力，包括羟基自由基和超氧阴离子自由基。在低剂量白光照射下（16 mW cm−2)，对耐甲氧西林金黄色葡萄球菌和耐药大肠杆菌的光动力杀灭效率高达99%。体内实验结果表明，TTCPy-3光敏剂在耐甲氧西林金黄色葡萄球菌和耐药大肠杆菌感染的伤口方面表现出优异的治疗性能，副作用可以忽略不计。因此，本项目的顺利实施为合理设计高性能I型聚集诱导发光光敏剂提供了有用的指导。