Functionalization of cationic porphyrins with peripheral platinum(II) complexes to optimize photodynamic therapy against Candida-associated infections: a focus on denture stomatitis and burn wounds

Abstract

Candida spp. are opportunistic pathogens associated with mucosal and cutaneous infections. Its increased resistance to antifungals has instigated the development of adjunct treatments, such as antimicrobial photodynamic therapy (aPDT). This study evaluated the antifungal effects of aPDT mediated by two tetra-cationic porphyrins with peripheral platinum(II) complexes (3-Pt and 4-Pt). A thorough investigation was performed using in vitro and in vivo assays to determine their antifungal activity on Candida albicans and toxicity in human cells. Next, specific models were employed to search for understanding of the action of aPDT on Candida-associated infections. As a result, a MIC value of 16 μmol/L was found for both porphyrins, with low toxicity to keratinocytes even in higher concentrations. Planktonic cultures of C. albicans treated by aPDT with 3-Pt achieved complete inhibition in 40 s, while 4-Pt reduced 1.3 Log10 (CFU) within 80 s. These effects were also extended to C. albicans biofilms, in which 3-Pt and 4-Pt reduced 4 and 0.8 Log10 (CFU), respectively. The mechanisms of action of 3-Pt were related to hyphae inhibition, increased ROS production, and cell wall damage. Finally, 3-Pt showed efficacy against denture stomatitis biofilms in a microcosm model and burn wounds in Galleria mellonella, indicating its potential for treating Candida-associated infections.