Overcoming HRP/TMB/H2O2 Limitations in LFIAs Using Cerium Oxide Nanozymes with Built-In Peroxidase Activity

Cerium oxide (CeO₂) nanozymes, also known as nanoceria have emerged as a versatile class of catalytic nanomaterials capable of mimicking key redox enzymes, including oxidases and peroxidases. Their tunable Ce³⁺/Ce⁴⁺ redox cycling, high density of oxygen vacancies, and exceptional resistance to thermal, pH, and storage stress distinguish CeO₂ from conventional enzyme labels, such as horseradish peroxidase (HRP). In immunoassays, CeO₂ enables H₂O₂-free TMB (3,3',5,5'-tetramethylbenzidine) oxidation, generating strong chromogenic signals with minimal background. Although CeO₂ nanozymes have been explored in colorimetric, chemiluminescent, and photoactive immunoassays, their integration into lateral flow immunoassays (LFIAs) remains limited, with only a few hybrid CeO₂-containing systems reported to date. This mini-review highlights the limitations of conventional peroxidase-based formats and explains how CeO₂'s redox cycling (Ce³⁺/Ce⁴⁺) and oxygen-vacancy-driven catalysis deliver stable, reagent-free signal amplification. Emphasis is placed on the synthetic control of CeO₂, conjugation chemistry with antibodies, and integration into LFIA architectures. CeO₂ enables hydrogen-peroxide-free colorimetric detection with improved robustness and sensitivity, positioning it as a promising catalytic label for point-of-care testing. However, it may aggregate in high-ionic-strength buffers, and its synthesis cost increases for highly uniform, vacancy-engineered materials. Surface functionalization with polymers or dopants and optimized dispersion strategies can mitigate these issues, guiding future practical implementations.