Regulating peroxidase‐mimic activity of iron oxide nanozymes through size modulation: electronic structure and specific surface area

Abstract Iron oxide nanoparticles (IONPs) with intrinsic peroxidase (POD)‐mimic activity have gained significant attention as nanozymes. Reducing sizes of IONPs is the mostly applied strategy to boost their enzymatic activity due to their high specific surface areas. Herein, we synthesized a series of uniformly sized IONPs ranging from 3.17 to 21.2 nm, and found that POD activity of IONPs is not monotone increased by reducing their sizes, with the optimal size of 7.82 nm rather than smaller sized 3.17 nm. The reason for this unnormal phenomenon is that electronic structure also had great influence on POD activity, especially at the ultrasmall size region. Since Fe 2+ are with higher enzymatic activity than Fe 3+ , 3.17 nm IONPs although have the largest specific surface area, are prone to be oxidized, which reduced their iron content and ratio of Fe 2+ to Fe 3+ , and consequently decreased their POD activity. By intentionally oxidized 7.82 nm IONPs in air, POD activity was obviously reduced, illustrating electronic structure cannot be overlooked. At the larger sized region ranging from 7.82 to 21.2 nm, oxidation degree of IONPs is similar, and surface electronic structure had a negligible effect on POD activity, and therefore, POD activity is predominantly influenced by specific surface area. By using the optimized 7.82 nm IONPs, tumor growth was obviously inhibited, demonstrating their potential in cancer therapeutics. Our results reveal that the designing of nanozymes should comprehensively balance their influence of surface electronic structure and specific surface area.