Abstract This study presents a new dopant-engineered nanotherapeutic approach by directly comparing the biological activities of yttrium-doped copper oxide (Y–CuO) and silver-doped zinc oxide (Ag–ZnO) nanoparticles produced through a controlled co-precipitation process. Extensive structural analyses (XRD, SEM, TEM, and EDX) confirmed high crystallinity, purity, and nanoscale sizes (∼10–50 nm). Both nanoparticles showed strong, dose-dependent anticancer and induced apoptosis in human cancer cell lines (HEPG-2, CACO-2, and A549), but they displayed different dopant-specific effects: Y–CuO NPs were more active against hepatocellular carcinoma (IC 50 = 79 μg/mL) and effectively inhibited inflammatory enzymes COX-2 (IC 50 = 4.73 μg/mL) and 5-LOX (IC 50 = 7.28 μg/mL), whereas Ag–ZnO NPs were more cytotoxic toward colon and lung cancers through ROS-driven mitochondrial apoptosis. Incorporating yttrium increased oxygen vacancies and defect density, encouraging cuproptosis-like apoptosis, while silver doping boosted ROS-mediated oxidative damage, revealing a dopant-dependent mechanistic difference. Both nanoparticles significantly increased Caspase-3 levels and decreased BCL-2 levels, confirming the involvement of mitochondrial apoptosis. Overall, these findings demonstrate, for the first time, that rare-earth versus noble-metal doping specifically regulates the balance between oxidative cytotoxicity and inflammation suppression, positioning Y–CuO NPs as a dual-action, redox-regulated nanotherapeutic and Ag–ZnO NPs as a ROS-driven cytotoxic agent. This discovery offers a transformative framework for designing dopant-controlled, multifunctional metal oxide nanomedicines for inflammation-related cancers.
khalifa et al. (Thu,) studied this question.