抗微生物药物耐受成为全球性问题，严重威胁公共健康。细菌生物膜的形成是产生耐药的重要因素，其机制有待阐明，目前临床缺乏有效诊疗生物膜感染的方法。研究发现生物膜胞外多糖在促进生物膜形成、维持生物膜结构、介导生物膜耐药等方面具有重要作用。本项目基于凝集素蛋白ConA靶向识别胞外多糖，通过生物正交反应在靶标ConA上共价连接具有独特光学特性的AIE分子和磁性Gd-DOTA，构建靶向多模态分子探针，以实现生物膜感染的可视化诊断；进一步巧妙利用酶响应自剪切策略，在生物膜微环境中高表达的β-内酰胺酶的水解底物上组装AIE光敏剂和群体感应抑制剂PD-12，构建新型诊疗一体化分子探针，以实现生物膜感染微环境刺激响应的多模态成像（光学、磁共振）和多模式（PDT和化疗）协同治疗。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，实现生物膜感染的诊断、治疗，为阐明其耐药机制提供理论基础和科学依据。

Antimicrobial tolerance has become a global problem that poses a serious threat to public health. The formation of bacterial biofilm is an important factor in the development of drug resistance. Its mechanism remains to be elucidated. At present, there is a lack of effective methods for the diagnosis and treatment of biofilm infection. The researches discover that biofilm extracellular polysaccharides play an important role in promoting biofilm formation, maintaining biofilm structure, and mediating biofilm resistance. This project is aim to visual diagnosis of biofilm infection by the construction of a novel targeted multimodal molecular probe based on ConA, an important lectin specifically identifying biofilm’s extracellular polysaccharides. The probe is covalently linked with AIE molecules with unique optical properties and magnetic Gd-DOTA by modern bioorthogonal reaction. Further, an enzyme response self-shear strategy is intelligent applied to assembly an AIE photosensitizer and quorum sensing inhibitor PD-12 on the hydrolyzed substrate of β-lactamase which highly expressed in biofilm microenvironment. The construction of new diagnostic and integrated molecular probes is prepared for the multimodal imaging (optical, magnetic resonance) and multimodal (PDT and chemotherapy) synergistic treatment of biofilm infection microenvironmental stimuli. This project is set on our great preliminary work, using the complementary advantages of multi-modal imaging technology to achieve the diagnosis and treatment of biofilm infection, and provide theoretical basis and scientific basis for elucidating its drug resistance mechanism.