Synthesis and Characterization of Mg-Doped CuO Nanoparticles and Their Enhanced Anticancer Efficacy Against HepG2 Liver Cancer Cells

The rising global incidence of hepatocellular carcinoma demands innovative therapeutic strategies. This study explores the enhanced anticancer potential of magnesium-doped copper oxide (Mg-doped CuO) nanoparticles, which were synthesized to improve upon the properties of undoped CuO nanoparticles. Mg-doped CuO nanoparticles with doping concentrations ranging from 1% to 5% were prepared using the co-precipitation method and thoroughly characterized by SEM, EDS, and FTIR. Their biological activity was evaluated against HepG2 liver cancer cells and normal human fibroblast cells. The MTT assay demonstrated a significant, concentration-dependent increase in cytotoxicity for Mg-doped CuO nanoparticles compared to undoped CuO, with the 3% Mg-doped CuO formulation showing the greatest potency (IC50 = 21.99 µg/mL at 48 h). Cell cycle analysis revealed that treatment with Mg-doped CuO nanoparticles, particularly at 3% and 5% doping concentrations, induced a substantial G2/M phase arrest, indicating a mechanism of action involving the disruption of cell division. Furthermore, all Mg-doped CuO nanoparticles exhibited markedly higher IC50 values in normal fibroblasts, confirming a favorable selective toxicity towards cancer cells. Apoptosis was identified as a key cell death pathway through acridine orange/propidium iodide staining. These results conclusively show that magnesium doping significantly augments the selective anticancer efficacy of CuO nanoparticles via cell cycle arrest and apoptosis induction, presenting a highly promising nanomaterial targeted liver cancer therapy.