Buzza HH, Alves F, Tome AJB, Chen J, Kassab G, Bu J, Bagnato VS, Zheng G, Kurachi C


DOI: 10.1073/pnas.2216239119

The management of biofilm-related infections is a challenge in healthcare, and antimicrobial photodynamic therapy (aPDT) is a powerful tool that has demonstrated a broad-spectrum activity. Nanotechnology has been used to increase the aPDT effectiveness by improving the photosensitizer’s delivery properties. NewPS is a simple, versatile, and safe surfactant-free nanoemulsion with a porphyrin salt shell encapsulating a food-grade oil core with promising photodynamic action. This study evaluated the use of NewPS for aPDT against microorganisms in planktonic, biofilm, and in vivo models of infected wounds. First, the potential of NewPS-mediated aPDT to inactivate Streptococcus pneumoniae and Staphylococcus aureus suspensions was evaluated. Then, a series of protocols were assessed against S. aureus biofilms by means of cell viability and confocal microscopy. Finally, the best biofilm protocol was used for the treatment of S. aureus in a murine-infected wound model. A high NewPS-bacteria cell interaction was achieved since 0.5 nM and 30 J/cm2 was able to kill S. pneumoniae suspension. In the S. aureus biofilm, enhanced efficacy of NewPS-aPDT was achieved when 100 µM of NewPS was applied with longer periods of incubation at the light dose of 60 J/cm2. The best single and double-session protocol reduced 5.56 logs and 6.03 logs, respectively, homogeneous NewPS distribution, resulting in a high number of dead cells after aPDT. The in vivo model showed that one aPDT session enabled a reduction of 6 logs and faster tissue healing than the other groups. In conclusion, NewPS-aPDT may be considered a safe and effective anti-biofilm antimicrobial photosensitizer.