DNA-capped iron oxide nanoparticles are nearly 10-fold more active as a peroxidase mimic for TMB oxidation compared to the naked nanoparticles. To understand the mechanism, the effect of DNA length and sequence is systematically studied, and other types of polymers are also compared. This rate enhancement is more obvious with longer DNA and in particular, poly-cytosine.Among the various polymer coatings tested, DNA offers the highest rate enhancement. Similar acceleration is also observed with nanoceria. On the other hand, when the positively charged TMB substrate is replaced by the negatively charged ABTS, DNA inhibits oxidation. Therefore, the negatively charged phosphate backbone and bases of DNA can increase TMB binding by the iron oxide nanoparticles and thus facilitating the oxidation reaction in the presence of hydrogen peroxide. Nanomaterials as enzyme mimics (nanozymes) have received considerable attention recently. 1-3 A wide range of nanomaterials including gold nanoparticles, 4, 5 metal oxides, 6-9 and carbon-based materials 10,11 have been reported to have oxidase, peroxidase, catalase, and superoxide dismutase like activity. Among these nanozymes, iron oxide nanoparticles (e.g. Fe3O4 NPs) are particularly interesting because of their unique magnetic properties and applications in magnetic resonance imaging, drug delivery, and separation. 2