Guanidine-Functionalized Pillar[5]arene Exhibits Antifungal Activity for Fungal Keratitis.

Fungal keratitis (FK) represents a severe infectious disease of the cornea, characterized by high incidence rates and a significant risk of vision loss, creating a substantial clinical need for novel therapeutic strategies. Addressing this challenge, we developed a water-soluble macromolecule, guanidine-linked pillar[5]arene (P5A-Gu), via click chemistry. P5A-Gu exhibited potent antifungal activity in vitro, characterized by rapid membrane penetration and complete fungicidal efficacy within 30 min at a low concentration of 1 μg/mL, alongside excellent biocompatibility. In murine FK models, P5A-Gu treatment significantly outperformed the clinical standard, voriconazole (Vor), in fungal clearance. Moreover, P5A-Gu effectively reduced corneal inflammation levels and accelerated the restoration of ocular surface tissue integrity. In summary, the macromolecule P5A-Gu shows highly effective antifungal properties and biocompatibility, positioning it as a promising candidate material for the treatment of FK.