生物质衍生碳点的制备及其光诱导抗菌性能研究

With the continuous emergence of drug-resistant microbial strains, antibiotic therapy has been unable to achieve excellent therapeutic effects on infectious diseases. Therefore, it is of paramount importance to develop highly effective bactericides and antibacterial techniques without multi-drug resistance. As one non-invasive treatment modes, photo-induced antibacterial therapies including photodynamic therapy and photothermal therapy show excellent prospects in the treatment of infectious diseases with prominent characteristics of minimal invasion, low toxicity, good selectivity, and repeatable treatment. More importantly, compared with conventional antibiotic therapy, pathogenic bacterium are less likely to produce drug resistance to photo-induced antibacterial therapies. Although carbon dots (CDs)-based phototherapy agents can effectively inactivate bacteria under light irradiation, their antibacterial applications have been greatly limited due to the complex synthetic route of precursors, high cost and weak selectivity and recognition. Therefore, in this project, with natural biomass as carbon source, a series of carbon dots (CDs) will be prepared for photo-induced bactericidal treatment. Furthermore, the in vitro and in vivo antibacterial activities of CD-based phototherapy agents will be in detail performed, as well as their antibacterial applications in wound dressings. The achievement obtained herein will not only further exploit the potentials of such carbon nanomaterials in the field of biomedical research, but also provide theoretical guidance for the design of novel high-efficient carbon-based antibacterial phototherapy agents.

随着耐药微生物菌株的不断涌现，抗生素在感染类疾病治疗方面已无法取得明显优势，因此探索新的抗菌药物和技术手段迫在眉睫。相较于传统抗生素治疗，光诱导抗菌疗法（包括光动力治疗和光热治疗）作为一种非侵入治疗模式，具有创伤性小、毒性低、选择性好、可重复治疗以及不易产生耐药性等优点，在抗菌领域表现出优异的应用前景。虽然现有碳点光疗制剂能够对致病菌实现有效的光诱导灭活，但仍面临着前驱体合成路线复杂、成本高昂和选择性识别弱等问题，在临床应用中受到极大限制。因此，本项目拟通过从自然界广泛存在的天然生物质中筛选碳源，制备廉价、水溶、低毒和高效的碳点光疗制剂，深入研究和探索其对耐药菌的光诱导灭活性能以及在伤口敷料中的应用拓展，希望进一步挖掘此类碳纳米材料在生物医学研究领域中的潜能，为设计新型高效碳基光疗制剂提供必要的理论指导。

光学疗法作为一种非侵入治疗模式，具有创伤性小、时空选择性好、无耐药性、毒性低等优点，在临床感染治疗中表现出巨大的潜力。2020年1月至2022年12月，在本项目的资助下，我们开展了一系列研究工作。比如，首次提出了电致发光诱导动力学治疗（Electroluminodynamic Therapy，ELDT）的新型抗菌策略，构建了负载有电致发光材料和光敏剂的离子导电水凝胶伤口敷料，在电场作用下可实现对致病菌的有效活性氧氧化灭杀。此外，在钛植入物表面构建了TNS-MPN-AMP纳米涂层，实现了对致病菌的物理穿刺/光热/化疗三重协同治疗的同时，促进植入物表面羟基磷灰石的形成以增强骨整合。.随着人口老龄化的加剧和饮食不规律、长期熬夜等不良生活方式的增加，恶性肿瘤发病率逐年上升，我国的癌症新发病例和死亡病例均为全球第一。基于此，在项目研究过程中，根据实验室的研究部署，我们对研究计划做了适当调整，在肿瘤光疗方面做了一部分工作。在国际上率先发展了I/II型活性氧可调的贯叶连翘衍生碳点，阐明了活性氧的调控机制，可用于红色荧光引导的线粒体靶向光动力治疗肿瘤。此外，还开发了其它一些纳米光诊疗剂。比如，负载竹红菌素衍生物的CaP纳米棒可用于近红外荧光成像引导的PDT。同时，我们还综述了近年来光疗技术在抗菌和肿瘤治疗等领域的应用进展等。.本项目在 Advanced Materials 和Biomaterials 等国际著名期刊上发表文章7 篇，其中1篇论文入选 ESI 高被引论文，申请中国发明专利3项，其中授权2项。