基于M13嵌合噬菌体的耐药病原菌感染精准诊断与可控治疗新方法研究

耐药病原菌感染是全球范围的重大公共安全问题，抗生素的长期滥用导致了多重耐药的“超级细菌”的产生。精准诊断病原菌灶点，尤其是区分细菌感染和其他病理在临床诊断上仍然是一项重大挑战，也是当前的研究重点。选择性地精准靶向去除感染病原菌而不改变微生物的群落结构，对有免疫缺陷和重症的患者至关重要。目前临床上还没有病原菌感染精准诊断和可控治疗一体化技术。我们前期发现M13嵌合噬菌体在不同环境中对宿主细菌有很强的特异性捕获能力，鉴于此本项目提出利用M13嵌合噬菌体递送复合上转换纳米材料，通过近红外荧光成像技术对感染区域进行特异性的无创成像。同时在808nm近红外光照射下，通过光热/光动力疗法特异性地杀死病原菌，而不影响正常组织和菌群。该方法创新性地提出了基于M13嵌合噬菌体靶向递送红细胞膜伪装的上转换纳米材料的新型噬菌体疗法，对于应对耐药性挑战有重要的科学意义和实际价值。

The infection of drug-resistant pathogens is a major public safety problem worldwide, and the long-term abuse of antibiotics has led to the emergence of multi-drug-resistant "superbugs". Accurate diagnosis of pathogenic bacterial infection foci, especially discrimination between bacterial infection and other pathologies remains a major challenge in clinical diagnosis and the focus of current research. Selectively and precisely targeted removal of infectious pathogens without altering the microbial community is crucial for immunocompromised and critically ill patients. At present, there is no integrated technology for accurate diagnosis and controlled treatment of pathogenic infection in clinical practice. We previously found that M13 chimeric phage can specifically target the host bacteria in various environment. Based on this we propose to deliver upconversion nanomaterials with M13 chimeric phage, and identify the infected areas with specific non-invasive near-infrared fluorescence imaging. Meanwhile, under the 808nm near-infrared laser light irradiation, the pathogens can be specifically killed by photothermal/photodynamic therapy without affecting the normal tissue and bacterial community. This method innovatively proposes a novel phage therapy strategy by using M13 chimeric phage as a vector for targeted delivery of erythrocyte membrane-camouflaged upconversion nanomaterials, showing great scientific significance and practical value to deal with the challenge of drug resistance.