Signal‐Amplified Point‐of‐Care Screening of Hepatocellular Carcinoma Enabled by an Electronically Coupled Au/PtIr Trimetallic Nanozyme

ABSTRACT Routine screening and longitudinal surveillance of hepatocellular carcinoma (HCC) require sensitive, on‐site analytical methods. Lateral flow immunoassays (LFAs) enable large‐scale screening but lack intrinsic signal amplification. Although nanozymes can enhance LFA readouts, their amplification remains constrained by inefficient hydrogen peroxide (H 2 O 2 ) activation. Herein, an electronically coupled Au/PtIr trimetallic nanozyme (Au/PtIr NPs) is constructed by decorating Au nanoparticle (Au NP) surfaces with island‐like PtIr alloy nanodomains. This architecture forms spatially adjacent dual‐site adsorption interfaces with heterogeneous electronic properties. Alloy‐induced interfacial electronic modulation synergistically optimizes H 2 O 2 adsorption and facilitates its homolytic O─O bond, selectively enhancing •OH generation and accelerating peroxidase‐like (POD‐like) catalytic kinetics. Integrated into an LFA platform, Au/PtIr NPs enable sensitive and reliable detection of α‐fetoprotein (AFP) in clinical samples, with a linear response from 0.2–1000 ng mL −1 and a limit of detection (LOD) of 57.7 pg mL −1 , which is 390‐fold lower than that of conventional Au NP‐based LFAs. The assay shows good agreement with clinical reference methods. The electronically regulated Au/PtIr interface maintains reliable amplification in complex biological matrices. Coupled with a simplified readout workflow, it enables minimally instrumented point‐of‐care detection. This electronic‐interface engineering approach provides a generalizable route to catalytic signal amplification for LFA‐based diagnostics.