Metformin‐Based Covalent Organic Frameworks With Excellent Biosafety and High Efficiency against Pathogenic Microorganisms

ABSTRACT The escalating public health security crisis caused by pathogenic microorganisms and the worsening antibiotic resistance urgently demand the development of antimicrobial materials with high efficiency and safety. Covalent organic frameworks (COFs) exhibit significant potential in photocatalytic antibacterial applications, but face challenges such as insufficient biosafety and difficulties in application translation. In this work, we first report two metformin‐based photoactive cationic MCOFs engineered for synergistic functionality and safety. They exhibit broad‐spectrum light absorption, efficient charge separation, and generate multiple ROS via Type I/II photodynamic, achieving >99 % inactivation of bacteria/viruses. Excellent biocompatibility with LD ₅₀ >5000 mg/kg is confirmed. Mechanistic studies based on molecular dynamics (MD) simulation and transcriptome results revealed a triple synergistic antibacterial pathway involving membrane targeting, ROS attack, and metabolic interference. Furthermore, we fabricated a COF/thermoplastic polyurethane (TPU) composite functional membrane, which exhibits >99 % antibacterial and antiviral efficiency, along with a notable 98.3 % inhibition rate against methicillin‐resistant Staphylococcus aureus (MRSA). This study not only provides a new design strategy for MCOFs with synergistically enhanced functionality and biosafety, but also offers a promising material platform for biomedical applications such as anti‐infection protection, wound healing, and the treatment of drug‐resistant bacterial infections.