Photodynamic inactivation of Candida albicans in different growth forms mediated by BODIPY derivatives

Candida albicans is an opportunistic fungal pathogen that normally exists as a commensal on human skin and mucosal surfaces, but under certain conditions it can develop virulence factors and exhibit antifungal resistance. Photodynamic inactivation (PDI) has emerged as a promising non-conventional approach to control this microorganism. In this study, the PDI activity of two BODIPY derivatives: a compound bearing a dimethylaminopropoxy group attached to a phenylene unit (BDP 1) and its dibrominated analogue (BDP 2) were evaluated against C. albicans in different growth forms. In planktonic cultures, 5.0 µM BDP 1 completely inactivated 1×10⁶ and 1×10⁷ CFU/mL after 30 min of white light irradiation (90 mW/cm²). The same effect was achieved with only 0.25 µM BDP 2 after an irradiation of 15 min. Additionally, a ~2 log reduction was observed in cultures containing 1×10⁸ CFU/mL treated with 5.0 µM BDP 2 and 30 min of irradiation. Mechanistic assays revealed that BDP 1 mainly acts via type I photoprocesses, while BDP 2 predominantly generates singlet molecular oxygen. In pseudohyphae suspended in PBS, 1.0 µM BDP 1 with 15 min of irradiation completely abolished viability, whereas BDP 2 required only 2 min for the same outcome. In biofilms, BDP 1 produced ~1.5 log viability reductions after 60 min of white light. In contrast, BDP 2 caused ~2 log and ~3 log reductions in 18 h old biofilms at 5.0 and 10.0 µM, respectively, and completely eradicated cells when 10.0 µM was applied during proliferation followed by 60 min irradiation. These findings highlight the superior performance of BDP 2 across all C. albicans morphologies, underscoring its potential as an effective photosensitizer for antifungal PDI strategies.