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Nanozymes are widely used in various applications as nanosized catalysts for replacing enzymes. An accurate estimation of the catalytic activity of nanozymes in real conditions is critical. In this article, for the first time, we systematically studied the effect of macromolecular molecules co-existing in the real system on the oxidoreductase (peroxidase, oxidase, and catalase)-mimicking nanozymes made of a gold nanoparticle core and a platinum shell, Prussian Blue, Mn2O3 and CoO nanoparticles. Comparisons were made with horseradish peroxidase. We distinguished two main mechanisms of the negative impact of macromolecules on nanozyme catalysis—slowed diffusion and surface shielding of nanoparticles. While the first mechanism is typical for enzymes, the second one is specific only for nanozymes. Understanding the mechanisms is essential for developing approaches to reduce the unavoidable impact of macromolecules for various analytical and biomedical applications.
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