The selective targeting ability of nanoparticles has overshadowed conventional cancer therapies. Recent studies have reported the anticancer potential of ZnO nanoparticles due to their high biocompatibility and selectivity. Through this study, the anticancer potential of biogenically synthesized glucose-capped (GC ZnO-NPs) and uncapped ZnO nanoparticles (UC ZnO-NPs) by aqueous leaf extract of Solanum nigrum has been assessed against the triple-negative breast cancer (MDA-MB-231) cell line through induction of apoptosis and the generation of reactive oxygen species (ROS). The GC ZnO-NPs nanoparticles exhibited controlled cytotoxicity (IC50=63.6 µg/mL) compared to UC ZnO-NPs(IC50=108.8 µg/mL), which may be due to surface passivation that might have modulated nanoparticle-cell surface interactions. These findings suggest that modifying the surface properties of ZnO nanoparticles with biocompatible moieties can enhance their therapeutic potential, offering promising avenues for personalized nanotherapeutics and precision oncology.