Structural engineering of 2D metal–organic framework-based nanomaterials for antibacterial applications

Drug-resistant bacterial infections are a growing crisis that severely threatens global public health, creating an urgent need for novel antibacterial strategies beyond traditional antibiotics. Two-dimensional (2D) metal-organic frameworks (MOFs) have emerged as a promising class of nanomaterials for antibacterial applications due to their high specific surface area, tunable porosity, structural diversity, atomically thin morphology, and exceptional structural tunability. However, the antibacterial activity of pristine 2D MOFs is often limited, making structural engineering essential for optimizing their performance. This review systematically summarizes recent advances in the structural engineering of 2D MOF-based nanomaterials for enhanced antibacterial therapy. Five primary engineering strategies are elaborated: dimension and morphology control, heterojunction construction, functional modification, element ratio regulation, and defect engineering. These approaches enable precise modulation of physicochemical properties, leading to significantly improved reactive oxygen species generation, charge separation, catalytic activity, and bacterial targeting. Subsequently, the diverse antibacterial mechanisms enabled by these engineered 2D MOFs are discussed, including photoresponsive therapy (photodynamic and photothermal), nanozyme-catalyzed therapy, controlled ion release, ultrasound-activated therapy, physical membrane disruption, and synergistic multimodal strategies. Finally, current challenges in clinical translation are critically analyzed, including synthesis scalability, long-term biocompatibility, targeting specificity, and stability, and an outlook on future directions is provided. By incorporating the latest developments in synthesis, mechanisms, and applications, this review seeks to provide guidance on the rational design of advanced 2D MOF-derived antibacterial agents and to inspire innovative approaches for combating drug-resistant bacterial infections.