Ziziphus nummularia-derived silver nanoparticles show potent anticancer activity against triple-negative breast cancer cells

Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor prognosis and limited targeted treatment options. Green-synthesized silver nanoparticles have emerged as promising therapeutic agents due to their biocompatibility and diverse biological activities. Aim The present study aimed to synthesize silver nanoparticles using Ziziphus nummularia aqueous leaf extract and evaluate their antioxidant and anticancer potential against MDA-MB-231 TNBC cells. Methodology Silver nanoparticles (ZNAgNPs) were synthesized through a green approach employing Ziziphus nummularia aqueous extract as a natural reducing and stabilizing agent. The synthesized nanoparticles were characterized using UV–Visible spectroscopy, FTIR, SEM, AFM, TEM/HRTEM, SAED, XRD, and zeta potential analysis. Antioxidant activity was determined by DPPH and H₂O₂ scavenging assays. Cytotoxicity against MDA-MB-231 cells was assessed by MTT assay, while apoptotic effects were investigated using DAPI staining, Rhodamine-123 assay, and DNA fragmentation analysis. Results Formation of ZNAgNPs was confirmed by a surface plasmon resonance peak at 416 nm. FTIR analysis indicated the involvement of phenolics, flavonoids, and other phytoconstituents in nanoparticle reduction and capping. Morphological studies revealed predominantly quasi-spherical nanoparticles with sizes ranging from 4 to 22 nm. SAED and XRD patterns confirmed their crystalline face-centered cubic structure, while a zeta potential value of –23 mV suggested moderate colloidal stability. ZNAgNPs exhibited strong concentration-dependent antioxidant activity and significant cytotoxicity against MDA-MB-231 cells, with an IC₅₀ value of 41.41 µg/mL, comparable to 5-fluorouracil. Mechanistic assays demonstrated nuclear condensation, mitochondrial membrane depolarization, and DNA fragmentation, indicating intrinsic mitochondria-mediated apoptosis. Conclusions Ziziphus nummularia aqueous extract represents an efficient and eco-friendly source for the synthesis of bioactive silver nanoparticles with potent antioxidant and anticancer properties. The novelty of this study lies in employing Ziziphus nummularia aqueous leaf extract as a green reducing/capping agent and demonstrating the resulting AgNPs against MDA-MB-231 cells, where such evidence has remained limited.