Optimized hybrid-chemical synthesis with morphology-controlled synthesis of copper-based nanomaterials as a response to emerging fungal drug resistance

The rapid development of nanoscience and nanotechnology has unlocked new possibilities in biomedicine, particularly in diagnostics, imaging, and targeted therapies. Among various nanomaterials, metallic nanoparticles, especially those based on copper, have attracted growing interest due to their unique physicochemical properties, ease of synthesis, and broad-spectrum antimicrobial activity. In this study, we report the synthesis and characterization of copper-based nanoparticles with significant antifungal activity against Candida spp., a genus responsible for a wide range of fungal infections, including life-threatening invasive candidiasis. Two distinct synthetic approaches were employed: a green, plant-mediated method to produce bimetallic Cu@Au nanoparticles with novel morphologies, and conventional synthesis routes for metallic Cu 2 O and Au nanoparticles. All nanoparticles were evaluated under the same experimental conditions to assess their antifungal efficacy against Candida albicans and Candida krusei , the latter being intrinsically resistant to fluconazole. In addition to their antifungal activity and moderate cytocompatibility at the effective concentrations, the Au@Cu nanoparticles exhibited intrinsic peroxidase-like catalytic activity, as demonstrated by colorimetric assays, UV–Vis spectroscopy, and steady-state kinetic analysis. The enzyme-like catalytic behavior suggests that oxidative catalytic processes may contribute to their antifungal mechanism, complementing the well-known antimicrobial effects of copper ions. Overall, our findings demonstrate that Au@Cu nanoparticles represent multifunctional nanomaterials with promising potential for antifungal and nanozyme-based biomedical applications, while highlighting the importance of sustainable synthesis strategies in the development of next-generation nanomedicines.