“Illuminated Glycoporphyrins”: A photodynamic approach for Candida albicans inactivation

Abstract

The continuous increase in the incidence of invasive mycoses, particularly those caused by Candida albicans, is a relevant health issue worldwide due to the lack of effective antifungals and the constant emergence of resistant strains. One of the most promising therapies to treat infections caused by resistant microorganisms is photodynamic inactivation (PDI). The development of novel photosensitizers (PSs) with suitable properties is a key factor to consider when optimizing this therapy. In this work, we designed, synthesized, and characterized four glycoporphyrins functionalized with S-galactose (acetylated and deacetylated) and varying the number of tertiary amino groups as precursors of cationic centers, which can be activated by protonation at physiological pH. The amino and glycosyl groups were introduced to enhance interaction with the microbial cell wall, increase hydrophilicity, and evaluate their combined effect on PS efficiency in photoinactivation. All derivatives presented the characteristic absorption and emission properties of the porphyrin macrocycle. Moreover, the glycoporphyrins were capable of generating singlet oxygen and superoxide anion radical. The photophysical and photodynamic properties were not affected by the different substitution patterns on the porphyrin core. PDI treatments of C. albicans cultures, treated with 5 μM of the PS and irradiated for 30 min, produced cellular inactivation of ∼3.5 log for glycoporphyrins with cationic centers. Furthermore, PDI of C. albicans mediated by glycoporphyrins was potentiated by the addition of KI. Under these conditions, a significant enhancement in cellular death was observed, achieving complete eradication of the treated cell suspensions. Moreover, glycoporphyrins containing pH-activable groups, combined with KI, showed outstanding efficacy against C. albicans pseudohyphae. These in vitro findings underscore the significant impact of substitution patterns on antimicrobial action. To our knowledge, this study marks the first application of glycosylated porphyrin derivatives containing pH-activatable cationic groups in the photoinactivation of C. albicans, paving the way for the development of novel derivatives with potential applications as effective antifungal PSs.