Defect-rich Ce–Zr–O solid-solution nanozymes with phosphatase activity for selective phosphate sensing

The phosphate ion (PO₄³⁻) is essential for growth, especially skeletal development. However, high PO₄³⁻ levels can signal health problems, such as hyperphosphatemia, which indicates chronic kidney disease due to reduced filtration, leading to serum phosphate buildup. Therefore, there is a pressing need for an accurate and convenient method for PO₄³⁻ analysis. Considering the significance of its detection, several techniques based on nanozymes have been employed, and among them, fluorometry is one of the most robust and efficient techniques. In terms of nanozymes, current developments suffer from low catalytic activity and non-specific inhibition. To address these issues, we present a solid-solution strategy for synthesizing Ce–Zr–O nanozymes with a defect-rich polycrystalline structure, providing a highly specific and efficient sensing platform. The approach is simple and cost-effective, yielding Ce–Zr–O nanozymes with excellent uniformity, controllable size, and morphology. Incorporating Zr⁴⁺ into the CeO₂ lattice induces abundant oxygen vacancies and structural heterogeneity, which synergistically enhance the phosphatase-like activity by enhancing Lewis acid catalysis and aiding the nucleophilic hydrolysis of 4-methylumbelliferyl phosphate (4-MUP). Notably, phosphate (PO₄³⁻) ions specifically bind to Zr sites, altering their electronic environments and attenuating catalytic performance. In exploiting this selective inhibition, we developed a fluorometric phosphate assay with high selectivity and sensitivity. The Ce–Zr–O nanozymes detected phosphate with a limit of detection (LOD) of 0.061 nM, allowing precise measurement of phosphate in urine. This study presents a generalizable defect-engineering method for Ce–Zr–O nanozymes, creating a reliable platform for interference-resistant biosensing in biological fluids. © 2026 Elsevier B.V.