Selective anticancer activity of doped zinc ferrite nanoparticles: A comparative study on human breast (MCF-7) and lung (A549) cancer cells

Abstract

This study systematically investigates the anticancer potential of zinc ferrite (ZnFe₂O₄) nanoparticles doped with aluminium (AZF), nickel (NZF), cobalt (CZF), and silver (SZF), with the goal of identifying the most effective formulation for cancer therapy. Based on the selective index and cytotoxicity screening across A549 (lung), MCF-7 (breast), and L929 (normal fibroblast) cell lines, silver-doped zinc ferrite (SZF) emerged as the optimal candidate. SZF exhibited the lowest LC₅₀ values in A549 (7.17 μg/mL) and MCF-7 (41.30 μg/mL) cells while maintaining comparatively higher LC₅₀ in L929 cells (172.90 μg/mL), indicating favorable cancer-selective cytotoxicity. Physicochemical characterization using XRD, FE-SEM, UV–Vis spectroscopy, and Williamson–Hall analysis confirmed phase purity, nanoscale crystallite size (7.6 nm for SZF), and minor dopant-induced structural perturbations. Biological evaluations demonstrated that SZF induced marked oxidative stress, with ROS levels increasing 3.4-fold in A549 and 12.4-fold in MCF-7 cells. This oxidative burden was associated with significant alterations in antioxidant enzyme activity, including catalase suppression in A549 cells and catalase elevation in MCF-7 cells. Flow cytometry revealed cell-cycle arrest, predominantly at the G0/G1 phase in A549 cells and G2/M arrest in MCF-7 cells, indicating cell-line-specific checkpoint responses. Annexin-V assays confirmed apoptosis as the primary mode of cell death. Furthermore, wound-healing assays demonstrated that SZF significantly inhibited cell migration in both cancer cell lines, suggesting potential anti-metastatic activity. Collectively, the results identify SZF nanoparticles as a promising multifunctional anticancer agent that exerts selective cytotoxicity through ROS generation, cell-cycle arrest, apoptosis induction, and migration inhibition.