Blue light-activated 5,10,15,20-tetrakis(4-bromophenyl)porphyrin for photodynamic eradication of drug-resistant Staphylococcus aureus

Photodynamic therapy (PDT) has emerged as an effective way to deal with drug-resistant bacterial infections. Especially, blue light (BL) mediated PDT (BL-PDT) presents unique advantages in the treatments of skin infection due to the strong light absorption of superficial skin, weak penetration of BL and little damage to deep tissues. However, the photosensitizers used for BL-PDT are very limited, and the ongoing development of novel BL photosensitizers is indispensable. Porphyrins are good sources for developing efficient photosensitizers. Herein, for developing more effective BL photosensitizers, five porphyrin derivatives that can be excited by BL [5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetrakis(4-bromophenyl)porphyrin (TBPP), 5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (TCPP), 5,10,15,20-tetrakis(4-fluorophenyl)porphyrin (TFPP), 5,10,15,20-tetrakis(4-iodophenyl)porphyrin (TIPP)] are subjected to the investigation of PDT against MRSA (methicillin resistant Staphylococcus aureus ). The results reveal that TBPP-mediated BL-PDT shows outstanding bactericidal effects. Mechanism studies show that TBPP + BL can induce reactive oxygen species (ROS) up-regulated in MRSA, rupture cell membrane, inhibit ATP (adenosine triphosphate) production and virulence factor expression. Furthermore, TBPP + BL effectively eliminates MRSA form biofilms, inhibits biofilm formation and disintegrates mature biofilms. More importantly, TBPP-PDT significantly accelerate mouse skin wound healing in a biofilm infection model. Our work offers new insights into the development of novel BL photosensitizers. Photodynamic therapy mediated by 5,10,15,20-tetrakis(4-bromophenyl)porphyrin (TBPP) effectively eliminates drug-resistant Staphylococcus aureus , inhibits biofilm formation and accelerates wound healing in a mouse model.