Abstract Surpassing natural enzymes in cost, stability and mass production, nanozymes have attracted wide attention in fields from disease diagnosis to tumor therapy. However, nanozymes intrinsically have low reaction selectivity, which significantly restricts their applications. A general method is reported to address this challenge by following a biomimetic operation principle of substrates channeling and screening. Two oxidase‐ and peroxidase‐like nanozymes (i.e., emerging N‐doped carbon nanocages and Prussian blue nanoparticles), were cascaded as a proof of concept to improve the reaction selectivity in transforming the substrate into the targeted product by more than 2000 times. The cascaded nanozymes were also adopted to a spatially confined microfluidic device, leading to more than 100‐fold enhancement of the reaction efficiency due to signal amplification.
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