Light Against Darkness: Novel Porphyrin and Chlorin-based Photosensitizers for Combating Multidrug-Resistant Bacterial Infections in the Post-Antibiotic Era

Multidrug-resistant (MDR) bacterial infections are a critical global health concern, necessitating alternative therapeutic approaches. This study investigates novel porphyrin and chlorin-based photosensitizers (PS) for antimicrobial photodynamic therapy (aPDT). Synthesized PS demonstrated high singlet oxygen yields (Φ∆ up to 0.93) and enhanced photostability. Their selective bacterial uptake enabled efficient photodynamic inactivation of both Gram-positive and Gram-negative pathogens. Pd(II)-porphyrin exhibited exceptional efficacy, achieving a 6-log reduction in S. aureus viability and significant biofilm disruption, as confirmed by fluorescence and electron microscopy. The cationic imidazolyl-porphyrin derivative showed remarkable E. coli PDI activity, further enhanced by cinnamaldehyde co-treatment, leading to a 7-log CFU reduction. In vitro 3D infection models revealed reduced bacterial adhesion, while in vivo murine wound models demonstrated bacterial clearance, minimal inflammation, and effective wound healing. These findings highlight the potential of optimized porphyrins and chlorins as next-generation antimicrobial agents, supporting their translational application in combatting MDR infections.