Exploring BODIPY derivatives as photosensitizers for antibacterial photodynamic therapy

Abstract

There is an urgent need to develop efficient and safe antimicrobials to augment traditional antibiotics for fighting drug-resistant bacteria. Antimicrobial photodynamic therapy (aPDT), is a promising antimicrobial stize antibiotic resistance and may reduce systemic side effects. Boron-dipyrromethene (BODIPY) is a type of photosensitizer (PSs) for aPDT with tunable structures and rational photophysical features. Herein, six kinds of BODIPY derivatives (BDP1-BDP6) modified with different atoms or groups such as iodine atoms, thiophene, cyano, phenyl, aldehyde and nitro groups were synthesized and their photophysical behaviors were characterized. The results indicated that BDP3, which had 2, 6-diiodo and 8-phenyl substitution, was the best PS candidate with the highest reactive oxygen species (ROS) generation efficacy. BDP3 and BDP5 could rapidly kill Staphylococcus aureus (S. aureus) with the minimum inhibitory concentration (MIC) of 10 nM upon illumination. They also possessed excellent biofilm inhibition ability against S. aureus and could efficaciously restrain the formation of bacterial biofilm. The results of Live/Dead staining assay and scanning electron microscopy (SEM) demonstrated that BDP3 destroyed the cell membrane structure of bacteria by generating ROS, which ultimately led to bacterial lysis and death. Finally, the biosafety evaluation toward the mouse fibroblasts (L929 cells) suggested BDP3 had good cytocompatibility. This work exhibits the great potential of rational designs of PS for aPDT applications.