细菌表面诱导多肽自组装用于细菌的检测及生长抑制

Bacterial infections cause significant mortality and morbidity worldwide despite the availability of antibiotics, clinical imaging tools which can image bacteria in vivo with accuracy and sensitivity are highly desirable. In this research proposal, we plan to use the strategy of ‘surface-induced self-asssembly’ to form molecular hydrogels at the surface of bacteria. These hydrogel can emit very strong fluorescence after the self-assembling and we will test their ability of imaging bacteria both in vitro and in vivo. We will combine molecules who can specifically interact with the surface of bacteria with peptide-based hydrogelators, then adding fluorophores with the character of aggregation-induced-emission or environment-sensitive. Such molecules can specifically bind to the surface of bacteria and then self-assembly into hydrogels, which can image bacterial infections with higher sensitivity and specificity. Meanwhile, we will investigate the survival and proliferation rates of bacteria after surface-induced self-assembling. The hydrogels at the surface of bacterial and its fluorescence intensity will be characterized by several techniques including cryo-TEM and confocal microscopy. The aims in this project are forming molecular hydrogels at different kinds of bacteria and provide an useful new strategy for bacteria imaging in vivo and antibiotic therapy, etc.

细菌感染导致的人类死亡数量庞大，目前临床医学亟需发展精确且灵敏度高的细菌体内成像技术用于细菌感染的早期诊断与快速治疗。本研究计划拟采用“表面诱导自组装策略”在细菌表面形成多肽小分子水凝胶，用于细菌的灵敏快速检测以及活性抑制。使用能够与细菌表面特异性结合的活性分子与短肽自组装分子相结合，并在其中引入聚集诱导发光（AIE）荧光分子或者环境响应型荧光分子，使其能够特异性地在细菌表面富集并自组装形成具有增强荧光的水凝胶，从而提高荧光成像的精确度和灵敏度。同时课题组还将考察细菌表面诱导形成的水凝胶后，细菌的生长状态和增殖率是否受到影响。课题组将采用冷冻透射电镜和激光共聚焦显微镜等多种技术手段证实小分子水凝胶在细菌表面的形成及其荧光性质。课题目标是成功实现细菌的表面诱导自组装，开发一种灵敏度高、靶向性好，同时能够起到抑菌作用的细菌荧光成像材料。本研究将为细菌的体内示踪和抗菌药物的开发等领域提供新思路。

在项目资助下，制备了几类带有荧光分子的自组装多肽，并分别用几种自组装多肽对细菌和细胞进行了检测和抑制存活率的实验，研究了自组装多肽性质与其在细胞表面及内部分布之间的关系。同时，还发展了两类基于自组装多肽的生物活性材料。重要研究结果包括：成功制备一系列可与细菌和细胞表面或内部细胞器结合的自组装多肽，完成其自组装和成胶性能等各类表征，获得小分子水凝胶在细菌表面诱导自组装的方法步骤；使用带有荧光的多肽成胶因子特异性地在细胞表面以及内部自组装形成小分子水凝胶，达到调控细胞活性，以及进行体内外荧光检测的目的。