Postmethylation of BODIPY-Based Covalent Organic Framework Nanostructures for Improving Photothermal and Photodynamic Bacterial Inactivation

The increasing resistance of bacterial pathogens to antibiotics poses serious threats to public health, exacerbating the challenge of treating infectious diseases. Antibacterial materials that integrate two or more therapeutic modalities concurrently have emerged as a viable alternative strategy to combat pathogenic bacteria. In this study, a postmethylation approach was employed to significantly enhance the photothermal and photodynamic activity of a photoactive antibacterial agent simultaneously. Using this method, a cationic covalent organic framework (COF) nanostructure, named IPB-COF, was easily fabricated through the postmethylation of a BODIPY-based COF obtained via the polycondensation of piperazine and dialdehyde-BODIPY through an aminal linkage. Besides improving the photothermal and photodynamic activities, the postmethylation also led to the formation of built-in quaternary ammonium cations, enhancing the adhesion capacity with bacteria. The resulting IPB-COF nanostructures exhibited enhanced synergistic photothermal and photodynamic therapeutic capabilities against both Gram-positive and Gram-negative bacteria upon visible light irradiation. It achieved rapid sterilization with an approximately 100% bactericidal ratio at a low dosage, significantly higher than that of the unmethylated sample (PB-COF). Additionally, in vivo assays demonstrated that IPB-COF nanostructures also possessed high efficiency and safe wound disinfection capacities, significantly accelerating the healing of infected wounds. Overall, this study proposes a simple yet robust method for the tunable preparation of COF-based antibacterial agents that can rapidly, safely, and synergistically combat pathogenic bacteria infections, circumventing antibiotic resistance.