Abstract
Ferrite nanoparticles (NPs) have emerged as promising candidates for cancer therapy. In this study, Mg-doped copper ferrite NPs, MgₓCu₁₋ₓFe(2)O(4) (x = 0.0, 0.5, and 1.0), were synthesized via a citrate–nitrate combustion method and evaluated for their anticancer potential. Structural and morphological characteristics were analyzed using powder X-ray diffraction, field-emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Cytotoxicity against human cancer cell lines was assessed using MTT and flow cytometry assays, along with analyses of reactive oxygen species (ROS) generation and apoptosis. Among the compositions studied, Cu(0.5)Mg(0.5)Fe(2)O(4) demonstrated the highest cytotoxic efficacy, with IC₅₀ values of 17.2 ± 0.15 µg/mL (PC-3) and 25.04 ± 0.28 µg/mL (Caco-2). Flow cytometric analysis revealed increased total apoptosis of 42.08% and 34.95% in PC-3 and Caco-2 cells, respectively. Gene expression analysis revealed downregulation of Bcl-2 and Cyclin D and upregulation of BAX, P53, and Caspase-3, indicating ROS-mediated mitochondria-dependent apoptosis. The enhanced anticancer activity of Cu(0.5)Mg(0.5)Fe(2)O(4) is attributed to its optimized size, surface charge, and composition, which promote cellular uptake, ROS generation, DNA damage, and interactions with cellular components. These findings highlight the potential of mixed-metal ferrite nanoparticles as effective nanomaterial-based cancer therapeutics.