Sun Sirong, Liu Xiangyu, Meng Xiangdan, Yang Zhou, Zhang Xueji, Dong Haifeng
School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, P. R. China.
Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 10083, P. R. China.
ACS Nano. 2025 Apr 22;19(15):15109-15119. doi: 10.1021/acsnano.5c02923. Epub 2025 Apr 10.
The development of reactive oxygen species (ROS)-based antibacterial strategies that overcome ROS's ultrashort diffusion distance and disrupt bacterial electron transfer represents a promising yet underexplored avenue for nonantibiotic therapies. In this study, we introduce an iron-copper bimetallic metal-organic framework (MOF) with peroxidase (POD)-like enzymatic activity engineered to integrate dual functionalities: bactericidal recognition and electron transfer disruption to synergistically enhance antibacterial efficacy. Mechanistic investigations reveal that boronic-acid-cis-diol interactions enable the MOF to selectively bind to bacterial membranes, where it generates localized ROS, effectively killing bacteria. Concurrently, the alignment of MOF energy levels with the bacterial redox potential facilitates efficient electron transfer from the bacterial membrane to the MOFs, disrupting membrane integrity and inhibiting critical processes such as electron transport and ATP synthesis. When incorporated into biodegradable microneedle patches, the MOF effectively penetrates biofilms and wound exudates, delivering potent antibacterial effects directly to infection sites while simultaneously promoting tissue repair. This strategic combination of bactericidal targeting, electron transfer disruption, and microneedle-mediated delivery highlights the potential of this approach to advance nonantibiotic antibacterial therapies.
开发基于活性氧（ROS）的抗菌策略，克服ROS超短的扩散距离并破坏细菌电子传递，这是一种有前景但尚未充分探索的非抗生素治疗途径。在本研究中，我们引入了一种具有过氧化物酶（POD）样酶活性的铁铜双金属金属有机框架（MOF），其经过工程设计以整合双重功能：杀菌识别和电子传递破坏，从而协同增强抗菌效果。机理研究表明，硼酸 - 顺二醇相互作用使MOF能够选择性地结合到细菌膜上，在那里产生局部ROS，有效杀死细菌。同时，MOF能级与细菌氧化还原电位的对齐促进了从细菌膜到MOF的有效电子转移，破坏了膜的完整性并抑制了诸如电子传输和ATP合成等关键过程。当MOF被整合到可生物降解的微针贴片中时，它能够有效穿透生物膜和伤口渗出物，将强大的抗菌效果直接传递到感染部位，同时促进组织修复。这种杀菌靶向、电子传递破坏和微针介导递送的策略性组合突出了这种方法推进非抗生素抗菌治疗的潜力。
