Photoinactivation of different growth forms of Candida albicans mediated by porphyrin-polyethylenimine conjugates

Candida albicans is a major cause of superficial candidiasis. Although antifungal therapies are widely available, their effectiveness can be compromised by biofilm formation and the emergence of drug resistance. Thus, photodynamic inactivation has emerged as a promising alternative approach for the treatment of fungal infections. In this work, two porphyrin-polyethylenimine conjugates were evaluated as photosensitizers to photoinactivate Candida albicans. Planktonic yeast suspensions (1 × 10⁶ CFU/mL) in phosphate-buffered saline (PBS) were treated with the conjugates (1.0 and 2.5 μM) for 30 min in the dark and subsequently irradiated with white light. Photoinactivation increased with both photosensitizer concentration and light fluence. Complete elimination of planktonic C. albicans was achieved with 2.5 μM TPPF₁₀TFA-PEI after 30 min of irradiation, whereas TPP₁₀CBZ-PEI produced a 2 log reduction in cell survival under the same conditions. Experiments using reactive oxygen species scavengers confirmed that singlet molecular oxygen was the predominant reactive species involved in the photoinactivation process for both conjugates. TPPF₁₀TFA-PEI was also effective against C. albicans pseudohyphae in PBS, with the reduction in viability increasing with both the conjugate concentration and irradiation time. Finally, the ability of the conjugates to inhibit C. albicans biofilm development on poly(vinyl chloride) (PVC) discs was evaluated by incorporating the photosensitizers during the biofilm proliferation phase. Under these conditions, TPPF₁₀TFA-PEI at 5.0 μM produced a 2 log reduction in biofilm viability, whereas TPP₁₀CBZ-PEI achieved a 1 log reduction. Therefore, these results demonstrate that TPPF₁₀TFA-PEI is an effective photosensitizing conjugate for the photoinactivation of C. albicans under planktonic, pseudohyphal, and biofilm growth conditions, highlighting its potential as a phototherapeutic agent for the treatment of fungal infections.