Porphyrin-based polymers for antifungal photodynamic inactivation of Candida albicans

Fungal infections are a growing health concern, associated with high mortality rates, elevated treatment costs, and an increasing number of hospitalized patients. Consequently, novel therapeutic strategies are urgently needed. In this work, two porphyrin-based polymers, PTPPF₁₆-DAB and PZnTPPF₁₆-DAB, were evaluated as photosensitizers for the photodynamic inactivation (PDI) of Candida albicans. These polymers are constructed from 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TPPF₂₀) or its Zn(II) complex (ZnTPPF₂₀) as porphyrinic units, and N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine (DAB) as a multifunctional crosslinker. Planktonic yeast suspensions (1 × 10⁶ CFU/mL) in PBS were treated with the polymers (2.5 or 5.0 µM) for 30 min in the dark. Both polymers rapidly bound to yeast cells within 5 min. Complete elimination of planktonic C. albicans was achieved at 5.0 µM after 30 min of irradiation. Experiments with reactive oxygen species scavengers confirmed that singlet molecular oxygen was the main species involved in the photoinactivation process. These polymers were also effective to photoinactivate C. albicans pseudohyphae in PBS, producing a concentration and time-dependent effect with both polymers. A complete loss of cell viability was observed when the cultures were treated with 5.0 µM. The most pronounced inhibitory effects on biofilms occurred when the polymers were incorporated during the proliferation phase. Against 18-h biofilms, PTPPF₁₆-DAB achieved a ~2.3 log reduction, whereas PZnTPPF₁₆-DAB was more effective during the adhesion phase, reducing viability by ~2 log. These results suggest that the antifungal performance of the polymers varies according to the metabolic activity and structural organization of C. albicans biofilms. The results indicate that both porphyrin-based polymers have potential applications as phototherapeutic agents for fungal inactivation under different culture conditions.