Ag–ZnO and Cu–ZnO Nanocomposites as Dual-Function Agents: Antifungal Activity and Cytotoxic Effects in MDA-MB-231 Breast Cancer Cells

Rising triple-negative breast cancer (TNBC) cases and Candida infection risks during chemotherapy demand novel therapies, with metal-oxide nanocomposites emerging as a promising solution. In this study, we synthesized Ag-ZnO and Cu-ZnO nanocomposites as established quantitative links between their physicochemical properties, ion release behaviour, and biological activity, evaluating antifungal effects against Candida albicans (ATCC 90028) and Saccharomyces cerevisiae (ATCC 9763), and their anticancer potential against MDA-MB-231 cells (ATCC HTB-26). The results revealed Ag (~13–19 nm) and Cu (~4–8 nm) nanoparticles dispersed in a ZnO matrix, with XPS confirming mixed Ag0/Ag(I)/Ag(III) and Cu(I)/Cu(II) speciation. Ag-ZnO NC exhibited strong antifungal activity (MIC = 25 mg L−1) against both fungi, while Cu-ZnO NC was only effective (MIC = 100 mg L−1) against S. cerevisiae. Aqueous release of Ag+ was ~2.6-fold higher than Cu2+. Ag-ZnO NC induced marked ROS generation (~6-fold higher than S. cerevisiae) and dehydrogenase inhibition (6.6- and ~20-fold, respectively). ATR-FTIR linked species-specific susceptibility to cell-wall architecture. SEM confirmed membrane destabilization and perforation. In MDA-MB-231, necrotic fractions reached ~9% and >40% for Ag-ZnO and Cu-ZnO, respectively. Both metal oxide nanocomposites (MONCs) act through ion release, revealing a selectivity window, especially for Ag-ZnO. Further studies on non-cancerous cells, ion-release kinetics, uptake and in vivo validation are essential to establish a therapeutic index.