Visualized Gallium/Lyticase-Integrated Antifungal Strategy for Fungal Keratitis Treatment

Fungal keratitis has been one of the common corneal infections that causes blindness, but an effective antifungal strategy remains a challenge. The exopolysaccharides both in the fungal cell walls and biofilms are a key that acts as a permeation barrier to weaken the therapeutic effect of antifungal agents. Herein, lyticase and gallium ions co-integrated nanosystems (MLPGa) are presented that can degrade exopolysaccharides and then effectively eradicate both planktonic Candida albicans and mature biofilms. The potential antifungal mechanism involves reactive oxygen species (ROS) production and metabolic interference of antioxidant-related genes, exopolysaccharide-related genes, iron-ion-utilization-related genes, fungal/biofilm-development-related genes, and virulence genes. Meanwhile, the Raman signals generated by the chelation between the nanosystems and the gallium ions provide a real-time visualization tool to monitor Ga release. Finally, the MLPGa-based antifungal strategy with good biocompatibility achieves a satisfactory therapeutic effect in a fungal keratitis mouse model. This study provides a unique approach to the effective treatment of fungal keratitis in clinical practice.