Fine-tuned Ce electron density directs H₂O₂ activation pathway in industrially employable CeO₂ nanozymes for ∼100% specificity and boosted activity in (Bromo)peroxidase mimicking

Nanozymes are promising alternatives to natural enzymes; however, most of them lack specificity, resulting in multiple enzyme-like activities that can interfere with one another in targeted applications. For example, CeO₂ nanozymes are often reported to exhibit both peroxidase (POD)-like and bromoperoxidase (BPO)-like activities. However, H₂O₂ inevitably competes in these reactions, reducing its utilization and performance in respective applications. Herein, we present a facile and scalable method for producing CeO₂ nanozymes with controllable reaction specificity. By adjusting the preparation atmospheres, the presence/ absence of coordinated N species allows for tuning the electron density of Ce sites, resulting in distinct H₂O₂ activation pathways and enabling nearly 100% mimicry of POD- and BPO-like activity. The absence of interference from one activity was demonstrated to intrinsically boost the other activity of CeO₂ nanozymes by over 1000%, far exceeding improvements reported in the literature. Additionally, our approach eliminates the need for labor-intensive purification, making it more cost-effective than natural enzymes and suitable for large-scale use. The optimized samples were then used to illustrate the importance of specificity control in enhancing performance for glucose detection and anti-bacterial/fouling applications. This work thus marks a milestone in artificial enzyme development, paving the way for the practical application of nanozymes. © 2026 The Authors.