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February 5, 2026Biosensors4 citationsOpen Access

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

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JLJohn HT Luong

Key Points

  • This review aims to explore the advantages of cerium oxide nanozymes over traditional peroxidase in lateral flow immunoassays.
  • Discussed redox cycling properties of cerium oxide nanozymes.
  • Highlighted oxygen-vacancy-driven catalysis for signal amplification.
  • Examined challenges with integration into lateral flow immunoassay formats.
  • Outlined strategies for surface functionalization and dispersion optimization.
  • CeO2 nanozymes facilitate hydrogen-peroxide-free colorimetric detection.
  • Improved signal robustness and sensitivity compared to traditional peroxidases.
  • Identified potential issues with aggregation in high-ionic-strength buffers.
  • Proposed methods to enhance uniformity and reduce synthesis costs.

Abstract

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.

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Cite This Study

John HT Luong (2026) studied this question.

synapsesocial.com/papers/69843583f1d9ada3c1fb462bhttps://doi.org/10.3390/bios16020096
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