Confinement‐Enrichment‐Driven Cascade Catalysis in a Self‐Assembled Nanozyme Reactor for Synergistic Antibiofouling and Biocorrosion Inhibition

ABSTRACT Marine biofouling, initiated by microbial colonization and biofilm formation, causes severe infrastructure deterioration and hydrodynamic drag. Although reactive oxygen/nitrogen species (ROS/RNS)‐mediated nanozymes offer a unique and highly promising platform for anti‐biofouling, their overall catalytic performance is often hindered by weakening interfacial catalytic kinetics within thick biofilms. Here we report a simple yet efficient self‑assembled CAGA nanozyme reactor that takes advantage of glucose as confined reactant to maintain high local reactant concentrations, and a branched copper‑L‑arginine (CA) core to facilitate interfacial mass transfer and substrate enrichment. More significantly, Au nanoparticles (AuNPs)‐decorated hyaluronic acid (HA) shell further enables microenvironment‐responsive activation of multienzyme‐mimicking activities. This intelligent design orchestrates a confinement‐enrichment‐catalysis 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‐Arg oxidation, promoting nitric oxide and peroxynitrite (NO and ONOO − ) formation. Antimicrobial experiments coupled with RNA‐sequencing transcriptomics validate this impressive antibacterial performance, attributed to the synergistic effects of amplified redox imbalance and cuproptosis‐like 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‐generation antibiofouling strategies.