Phytolectin Potentiates Copper Sulfide Nanoparticles Anticandida Activity Through Enhanced ROS Production

Fungal infections caused by Candida albicans are challenging to treat with antifungal drugs due to the emergence of antimicrobial-resistant strains, necessitating the development of innovative therapeutic methods. The present study demonstrates that cationic copper sulfide nanoparticles (cCuS) synthesized using [2-((N-(2-hydroxyethyl)palmitamido)methyl)-1-methylpyridin-1-ium iodide] exhibit increased efficacy against C. albicans when delivered using Jacalin, a lectin from jackfruit that binds to cell surface glycans. The requirement of cCuS to kill was reduced twofold when delivered through Jacalin. Membrane integrity assays showed that JcCuS caused only minimal membrane permeabilization, indicating that membrane disruption is not the primary mechanism of action. Instead, JcCuS significantly increased intracellular reactive oxygen species (ROS), suggesting that oxidative stress plays a central role in its antifungal activity. Elevated ROS levels were markedly reduced by the antioxidant N-acetyl cysteine, confirming ROS-mediated toxicity. Excess ROS also induced apoptosis-associated nuclear condensation and disrupted fungal redox homeostasis by significantly decreasing intracellular reduced glutathione levels. In addition, JcCuS effectively inhibited hyphal growth and filamentation, key virulence factors required for C. albicans pathogenesis. These findings demonstrate that lectin-mediated delivery enhances the efficacy of cCuS nanoparticles by promoting ROS-dependent fungal cell death while preserving membrane integrity, representing a promising strategy for developing targeted antifungal nanotherapeutics.