Green Ziziphus nummularia gold nanoparticles: antioxidant and anticancer activity in TNBC.

Triple-negative breast cancer (TNBC) remains one of the most aggressive breast cancer subtypes with limited targeted therapeutic options, highlighting the need for innovative, biocompatible treatment strategies. Plant-mediated green synthesis offers a sustainable route for gold nanoparticle (AuNP) fabrication with enhanced biological functionality. In this study, Ziziphus nummularia ethanolic extract (ZNE) was employed as a reducing and capping agent to synthesize stable, crystalline, and predominantly spherical gold nanoparticles (ZNE-AuNPs). Comprehensive physicochemical characterization confirmed successful nanoparticle formation and phytochemical capping. Importantly, this work provides novel biological and mechanistic insights into the anticancer effects of ZNE-AuNPs specifically in TNBC. ZNE-AuNPs exhibited notable antioxidant activity and significantly reduced the viability of MDA-MB-231 TNBC cells in a concentration- and time-dependent manner. For the first time, the anticancer activity of ZNE-AuNPs in TNBC was mechanistically linked to the suppression of cellular proliferation (decreased Ki-67), induction of apoptosis (modulation of BAX, BCL-2, and caspase-3), and inhibition of ERK phosphorylation, implicating the MAPK/ERK signaling pathway. Taken together, these findings support Ziziphus nummularia-derived AuNPs as a sustainable nanotherapeutic platform and establish their previously unexplored mechanistic relevance in TNBC.