CeO₂ nanozymes: how do crystal facets regulate enzymatic specificity?

Nanozymes have emerged as promising alternatives to natural enzymes, yet their catalytic performance often falls short of biological counterparts due to poor mechanistic understanding. Among them, CeO₂ stands out for its ability to mimic multiple enzymes, including alkaline phosphatase (ALP), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and bromoperoxidase (BPO). However, its poor substrate specificity and, in particular, the competition for a single substrate, H₂O₂, across POD, CAT, and BPO-like activities significantly hinder its practical applications. While Ce is generally considered the active species, the challenge lies in the coexistence of multiple Ce species with distinct reactivity and abundance in CeO₂ nanozymes lacking precise surface control, each contributing differently to these enzymatic reactions. This complexity is amplified by variations in synthesis methods, surfactants, dopants, and other parameters adopted in the literature, which make qualitative and quantitative comparisons of Ce species very difficult. Even for well-defined CeO₂ shapes enclosed dominantly by a specific facet, conventional surface techniques still lack the resolution to differentiate Ce species across facets/shapes, resulting in conflicting correlations despite the use of the same synthesis methods. Here, we critically review the current understanding of CeO₂ surface chemistry, emphasizing facet-dependent effects and characterization limitations. Using advanced surface techniques on well-defined CeO₂ shapes, we summarize recent findings on how distinct Ce sites, with varying coordination/electronic structures, direct the activation of phosphorylated compounds (ALP-like activity) and H₂O₂ (POD/CAT- and BPO-like activities). These insights have enabled spatial decoupling of multiple enzyme-like activities on rod-shaped CeO₂ and scalable synthesis with tunable specificity. This feature article thus highlights the value of atomic-level surface characterization for reliable catalytic correlation and offers a rational framework for designing next-generation nanozymes with optimized specificity and performance.