Photodynamic Inactivation of <i>Staphylococcus aureus</i> and Biomolecules by Free and Encapsulated Indium(III) Phthalocyanines in PHB Nanoparticles: The Influence of the Position of the Coumarin Group

Antimicrobial photodynamic therapy (APDT) is a promising alternative to inactivating resistant microorganisms. Metallic phthalocyanines (Pc) substituted with coumarin groups exhibit favorable photophysical properties for APDT; however, their hydrophobicity limits administration. This study investigates indium(III) Pc substituted with 7-oxy-3-(3',4',5'-trimethoxyphenyl)coumarin at nonperipheral (<b>3nInOAc</b>) and peripheral (<b>4nInOAc</b>) positions, both in their free form and encapsulated in polyhydroxybutyrate nanoparticles, for the photodynamic inactivation of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA) bacteria. The photodynamic activity was also assessed through the photooxidation of tryptophan and bovine serum albumin. Theoretical calculations and molecular docking were performed to corroborate the experimental results, investigating the influence of molecular structure on the photodynamic and antimicrobial performance of Pc-loaded nanoparticles as well as their nanoparticulate properties. Overall, both free and encapsulated Pc were capable of photooxidizing biomolecules and exhibited moderate antimicrobial activity, with <b>4nInOAc</b> demonstrating superior efficacy, achieving an average reduction of 2 logs (99%) in MSSA and MRSA colonies.