Impact of Metal-Functionalized Fullerenes on the Proliferation of Pathogenic Fungi

Given the trajectory and prevalence of multidrug-resistant (MDR) organisms like Candida auris, the dearth of available antifungal drugs and the global need for effective therapeutics, the exploration of safe antifungals with broad-spectrum potential and novel antimicrobial mechanisms is imperative for future treatment strategies. Herein, the broad-spectrum potential of previously synthesized silver and copper coordinated chlorine functionalized fullerene nanoparticles (Ag-C60-Cl and Cu-C60-Cl) against two clinically significant fungal pathogens, Candida albicans and C. auris is investigated. The experimental results show enhanced antifungal activity of Ag-C60-Cl compared to Cu-C60-Cl, C60-Cl, and fluconazole. The minimum inhibitory concentrations (MIC) of Ag-C60-Cl and Cu-C60-Cl are 15.62 and 250 μg/mL, respectively, against C. albicans. Notably, the MIC of the Ag-C60-Cl against C. auris is 3.9 μg/mL, whereas the MIC of Cu-C60-Cl is 250 μg/mL. Analysis of fungal growth kinetics shows that Ag-C60-Cl significantly delayed the growth of C. albicans and suppressed the growth of C. auris. Mechanistic studies highlight that Ag-C60-Cl produced higher reactive oxygen species (ROS) and triggered catalase enzymes by acting as oxidants. Additionally, the NPs exhibited physical interactions with yeast cells, indicating a dual mode of action. These findings establish the potential of Ag-C60-Cl as a new and potentially transformative antifungal strategy against two clinically significant pathogens.