Eradication of Fungi Using MoSe₂/Chitosan Nanosheets

Antifungal drug resistance is an increasingly significant threat to humans, livestock, and crops. Recent studies have shown nanomaterials as promising alternatives in combating drug-resistant pathogens. Here, we show that molybdenum diselenide (MoSe₂) nanosheets dispersed in the cationic polymer chitosan (CS) exhibit exceptional antifungal activity. The MoSe₂/CS nanosheets provide minimum inhibitory concentrations (MICs) between 0.78 and 37.5 μg ml^–1 against a variety of unicellular fungal strains and demonstrate minimum fungicidal concentrations (MFCs) from 0.5 to 75 μg ml^–1 for diverse unicellular and filamentous strains. Furthermore, we demonstrate the ability of MoSe₂/CS to eradicate increasingly prevalent and highly multi-drug-resistant (MDR) fungi Candida auris strains with MICs of 25 to 50 μm ml^–1 and MFCs of 37.5 to 150 μm ml^–1. The effective antifungal activity of MoSe₂/CS was observed after an incubation time of 3 h, which is faster than the time needed for other nanomaterial-based antifungal agents incorporating graphene, two-dimensional (2D) nanomaterials, or silver nanoparticles. MoSe₂/CS also showed high biocompatibility and was benign toward human red blood cells and human embryonic kidney cells. Electron microscopy and confocal optical microscopy show that fungal cells treated with MoSe₂/CS nanosheets exhibit morphological deformities, ruptured cell walls and interior voids, and metabolic inactivation. Mechanistic investigations revealed that treatment with MoSe₂/CS triggers complete membrane depolarization and membrane disintegration within 3 h. Hence, this work demonstrates that the biocompatible nanomaterial MoSe₂/CS is a highly effective alternative antifungal agent against many kinds of pathogenic fungi including MDR strains.