Biomedical utility of zinc and copper mediated cerium oxide nanoparticles

Breast cancer remains a leading cause of cancer-related death worldwide, motivating the development of nanobiomaterials that exploit tumour-associated redox vulnerabilities while limiting systemic toxicity. Cerium oxide nanoparticles (CeO₂, CNPs) are promising in this context due to their reversible Ce³⁺/Ce⁴⁺ redox cycling and oxygen vacancy mediated enzyme-mimetic activity, which enables microenvironment dependent modulation of reactive oxygen species. However, defect driven catalytic plasticity complicates predictive design for biological applications. Here, Zn- and Cu-doped CNPs (5-20 mol%) were synthesized via forced hydrolysis and characterized using XPS, UV-Vis spectroscopy, XRD, TEM, dynamic light scattering, and zeta potential analysis, confirming fluorite structure with crystallite sizes of ∼4-7 nm and no secondary crystalline phases detectable by XRD, consistent with successful dopant incorporation. XPS analysis revealed dopant dependent differences in surface redox chemistry, with Zn- and Cu-doped CNPs exhibiting distinct Ce³⁺ fractions and redox active surface states. Enzyme-mimetic assays showed that Zn-doped CNPs substantially enhanced superoxide dismutase-like activity at low dopant levels while suppressing catalase-like activity, whereas Cu-doped CNPs significantly increased catalase-like activity at higher dopant loadings, indicating distinct catalytic fingerprints at the nano-bio interface. Normal human unbillical vein endothelial cells (HUVECs) exhibited an increase in cell number at low concentration of CNPs and doped nanoparticles, whereas Zn and Cu-doped CNPs showed significant reduction in cell number at higher concentrations. Collectively, these results demonstrate dopant-gated control of surface redox states as a strategy to tune the catalytic behavior of nanoceria and highlight the potential of doped CNPs as programmable redox-active nanobiomaterials with preferential in vitro cytotoxicity toward cancer cells.