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Although reactive oxygen\/nitrogen species (ROS\/RNS)\u2010mediated nanozymes offer a unique and highly promising platform for anti\u2010biofouling, their overall catalytic performance is often hindered by weakening interfacial catalytic kinetics within thick biofilms. Here we report a simple yet efficient self\u2011assembled CAGA nanozyme reactor that takes advantage of glucose as confined reactant to maintain\u00a0high local reactant concentrations, and a branched copper\u2011L\u2011arginine (CA) core to facilitate interfacial mass transfer and substrate enrichment. More significantly, Au nanoparticles (AuNPs)\u2010decorated hyaluronic acid (HA) shell further enables microenvironment\u2010responsive activation of multienzyme\u2010mimicking activities. This intelligent design orchestrates a confinement\u2010enrichment\u2010catalysis cascade process inside the CAGA nanozyme reactor, thus amplifying its ROS\/RNS output for biofilm eradication. Density functional theory (DFT) confirms Cu active sites lower the energy barrier for L\u2010Arg oxidation, promoting nitric oxide and peroxynitrite (NO and ONOO\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) formation. Antimicrobial experiments coupled with RNA\u2010sequencing transcriptomics validate this impressive antibacterial performance, attributed to the synergistic effects of amplified redox imbalance and cuproptosis\u2010like pathways. This hybrid CAGA nanozyme reactor remarkably suppresses microbiologically influenced corrosion (MIC) and exhibits excellent antifouling performance in practical coatings, providing a rational paradigm for developing next\u2010generation antibiofouling strategies.\n                  <\/jats:p>","DOI":"10.1002\/adma.74995","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:45:28Z","timestamp":1789400728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Confinement\u2010Enrichment\u2010Driven Cascade Catalysis in a Self\u2010Assembled Nanozyme Reactor for Synergistic Antibiofouling and Biocorrosion Inhibition"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7372-3927","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Digital Steel School of Materials Science and Engineering Northeastern University  Shenyang P. 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