Department of Laboratory Medicine, Institute of Precision Medicine The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, 1510080, Guangzhou, China.
Department of Chemical and Biomolecular Engineering, National University of Singapore, 117585, Singapore, Singapore.
Angew Chem Int Ed Engl. 2024 Oct 7;63(41):e202408918. doi: 10.1002/anie.202408918. Epub 2024 Sep 10.
The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the Cu-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of Cu to Cu through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.
抗生素的过度和长期使用导致了耐药性金黄色葡萄球菌菌株的出现和潜在的与肠道菌群失调相关的疾病，因此需要探索替代的治疗方法。在这里，我们提出了一种光激活纳米催化剂，用于通过光氧化还原催化点击反应原位合成抗菌剂，实现对金黄色葡萄球菌皮肤感染的精确、靶向消除。亚甲蓝（MB）是一种市售的光敏剂，被包裹在基于铜的金属有机骨架 MOF-199 中，并进一步用 Pluronic F-127 包裹，形成光响应纳米催化剂 MB@PMOF。在红光照射下，MB 参与光氧化还原催化循环，由 MOF-199 结构中的 1,3,5-均苯三甲酸根（BTC）盐驱动。这种光激活的 MB 随后通过单电子转移（SET）过程将 Cu 还原为 Cu，在生理条件下有效地引发点击反应，形成活性抗菌剂。体外和体内实验结果都证明了 MB@PMOF 催化药物合成在抑制金黄色葡萄球菌（包括其耐甲氧西林菌株）方面的有效性，从而加速严重细菌感染的皮肤愈合。这项研究引入了一种控制、原位药物合成的新设计范例，为实现精确治疗细菌感染而不产生不良副作用提供了一种有前途的替代方案。
