Biomedical utility of zinc and copper mediated cerium oxide nanoparticles

Abstract

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.