A novel 450 nm blue laser-mediated sinoporphyrin sodium-based photodynamic therapy inactivates Cutibacterium acnes through stress-mediated metabolic alterations.

Acne vulgaris is a chronic inflammatory skin disease closely linked to the abnormal colonization and proliferation of Cutibacterium acnes (C. acnes). Photodynamic therapy (PDT) has emerged as an ideal treatment. However, it still faces challenges such as low reactive oxygen species (ROS) production rates with porphyrin-based photosensitizers and low activation efficiency of conventional red light. This study investigated the in vitro and in vivo bactericidal effects of sinoporphyrin sodium (DVDMS) combined with a novel 450 nm blue laser-mediated photodynamic therapy (BL-PDT) on C. acnes, and explored the potential mechanisms, focusing on energy metabolism. In our results, C. acnes showed a time-dependent uptake of DVDMS, and BL-PDT demonstrated an excellent bactericidal effect on C. acnes in vitro by inducing a large amount of ROS production. RNA sequencing and metabolomic analysis revealed that BL-PDT inhibited C. acnes carbon metabolism while initially enhancing respiration; however, both fermentation and respiration were suppressed after 2 h, and ATP declined time-dependently in this process. Ultimately, the combined effects of ROS-induced damage (from DVDMS and enhanced respiration) and ATP depletion led to bacterial death. Similarly, in vivo experiments confirmed the favorable therapeutic efficacy and safety of BL-PDT in a rat model of acne. In conclusion, DVDMS-based BL-PDT may be a safe and effective new treatment against acne. Thus, our results provide compelling evidence for using DVDMS and BL-PDT in acne treatment.