Effect of porphyrin metalation and synergistic combination with fluconazole in antifungal PDT against <i>Candida spp</i>

Candidiasis, a common fungal infection, presents significant treatment challenges due to the increasing resistance of Candida species to conventional antifungal medications. Photodynamic antimicrobial chemotherapy (PACT) offers a promising alternative by utilizing photosensitizers activated by specific wavelengths of light to generate reactive oxygen species (ROS), which effectively eradicate pathogens. This study investigated the efficacy of PACT using porphyrin-based photosensitizers, including free base and metallated porphyrins (zinc, indium, and gallium derivatives), both alone and in combination with fluconazole, against two Candida strains: Candida albicans ATCC 10231 and Candida krusei ATCC 6258. The photosensitizers were activated using a 430 nm LED, delivering a fluence of 180 J/cm 2 . Post-treatment, the antimicrobial effect was assessed by quantifying colony-forming units (CFU). P-InCl exhibited potent antifungal activity, achieving a 5-log reduction in colony-forming units (CFU) for Candida albicans (C. albicans) and a 4.5-log reduction for Candida krusei (C. krusei) following PACT alone. When combined with fluconazole, P-InCl demonstrated enhanced efficacy, achieving complete eradication of C. albicans within 15 minutes and a 5-log reduction for the fluconazole-resistant C. krusei within 30 minutes. These findings highlight the potential of PACT, particularly when combined with antifungal agents, as an effective strategy for treating resistant or persistent Candida infections, suggesting a path toward clinical implementation in antifungal therapies.