Dodonaea viscosa-derived gold nanoparticles exhibit differential effects across breast cell models and intracellular localisation in MDA-MB-231 cells

Breast cancer remains a major malignancy, with triple-negative breast cancer (TNBC) representing an aggressive subtype with limited therapeutic options. This study investigated the synthesis, physicochemical properties, and biological activity of Dodonaea viscosa-derived gold nanoparticles (DV-AuNPs). Synthesis was optimised for reaction temperature, extract concentration, and extract-to-gold chloride ratio. DV-AuNPs were characterised using ultraviolet–visible spectroscopy, dynamic light scattering, X-ray diffraction, Fourier-transform infrared spectroscopy, and electron microscopy, and their colloidal stability was assessed in biologically relevant media over two weeks. The nanoparticles were predominantly spherical (19.6 ± 3.6 nm) and exhibited surface functionalisation with plant-derived compounds. Cellular metabolic activity/viability assessment revealed differential responses across breast-cell models: MDA-MB-231 cells demonstrated concentration-dependent sensitivity to DV-AuNP exposure, whereas MCF-7 and non-tumorigenic MCF-12A cells were comparatively less responsive under the tested conditions. In MDA-MB-231 cells, DV-AuNP treatment markedly suppressed clonogenic capacity, while functional assays revealed limited effects on migration and epithelial-to-mesenchymal transition (EMT)-associated proteins. Transmission electron microscopy demonstrated intracellular localisation of electron-dense particles consistent with DV-AuNPs. To the best of our knowledge, this study provides the first integrated evaluation of DV-AuNPs in a TNBC model encompassing physicochemical characterisation, colloidal stability, differential cellular responses, clonogenic capacity, migration, EMT-associated proteins, and intracellular localisation. Altogether, these findings demonstrate cell-line-dependent biological responses to DV-AuNPs and support their continued investigation as biologically functionalised gold nanoparticles for breast-cancer applications. Further studies are required to define the underlying mechanisms and evaluate activity across additional TNBC models.