Evaluation of the antivirulence and anticancer potential of green-synthesized silver/zinc oxide nanocomposites against methicillin-resistant Staphylococcus aureus and melanoma cells

The escalating incidence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates novel therapeutic strategies targeting antibiotic resistance and biofilm formation. Silver/zinc oxide nanocomposites (Ag/ZnO NCs) were green-synthesized using Pistacia atlantica leaf extract. Comprehensive characterization confirmed spherical nanocomposites with an average size of 18.1 nm and uniform distribution. The NCs exhibited strong antimicrobial activity with MICs of 0.25 and 0.125 mg/mL against clinical MRSA and S. aureus ATCC 6538, reducing biofilm formation by ~ 98%. Treatment at 1/2× MIC significantly downregulated biofilm-associated genes (icaA, icaD, clfA, clfB, fnbA) and the mecA resistance gene. Ag/ZnO NCs showed dose-dependent anticancer effects (IC₅₀ = 22.36 µg/mL) against melanoma A375 cells with lower cytotoxicity toward normal fibroblasts (IC₅₀ = 48.79 µg/mL) and notable antioxidant activity. These findings establish rationale for in vivo validation of green-synthesized Ag/ZnO NCs as multifunctional antimicrobial and anticancer agents.