INTRODUCTION Cascade catalytic reac

INTRODUCTION Cascade catalytic reaction systems in living organisms have evolved by confining multiple enzymes within subcellular compartments to ensure accurate signal transduction and effective metabolism (1). Confined cascade reactions gain advantage over conventional multistep reactions by reducing diffusion barriers, enhancing local concentrations of intermediates, and improving atom economy of overall reactions (2). Inspired by the advantages of these systems, substantial efforts have been made to organize enzymes on different scaffolds to mimic these efficient cascade systems (3–6). However, because of the high cost, low stability, and potential immunogenicity of scaffold­ supported enzyme cascades, the design and utility of natural enzyme– based cascade reactions in biomedical applications (especially in vivo therapeutics) are limited. To tackle these limitations, enzyme mimics have been exploited to construct cascade reactions. Among these, nanozymes, enzyme­ like nanomaterials, have received particular interest due to low cost, high stability, multifunctionality, and ease of large­scale production (7–20). Numerous efforts have explored the combination of nanozymes with natural enzymes to mimic cascade reactions (21–23), with one example being the combination of glucose oxidase and a peroxidase mimic for the selective detection of glucose (21). However