pH‐Responsive Nanoscale Mixed Ligand Metal Organic Framework as a Carrier for Photosensitizer in Targeted Antibacterial Photodynamic Therapy

The escalating multidrug‐resistant bacterial infections underscore the urgent need for alternatives to conventional antibiotics. Antimicrobial photodynamic therapy emerges as a promising strategy, leveraging light‐activated photosensitizers like methylene blue (MB) to generate bactericidal reactive oxygen species (ROS) that disrupt microbial membranes and DNA. This approach minimizes resistance development due to the nonspecific action of ROS and demonstrates efficacy against both Gram‐positive and Gram‐negative pathogens. A pH‐responsive mixed‐ligand metal‐organic framework (ML‐MOF) is synthesized as a nanocarrier for MB. Encapsulation of MB into ML‐MOF (MB@ML‐MOF50) resulted in a loading capacity of 29.67%, with a controlled and sustained release profile of 85% at pH 5.1 (infection‐mimicking conditions). MB@ML‐MOF50 exhibited twice the singlet oxygen generation efficiency (S = 0.2098) compared to free MB (S = 0.1058), confirming enhanced photodynamic activity. MB@ML‐MOF50 under 650 nm laser irradiation achieved complete bacterial inhibition (0% survival) at 25 µM, surpassing free MB. Biofilm eradication studies using the crystal violet (CV) assay revealed 37.26% inhibition of Escherichia coli ( E. coli) biofilm and 25.42% inhibition of Staphylococcus aureus (S. aureus) biofilm after 15 min of laser exposure compared to a nonirradiated control, indicating the potential for disrupting persistent infections. MB@ML‐MOF50 is a promising multifunctional nanoplatform for targeted, pH‐responsive, and enhanced photodynamic antibacterial therapy.