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

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.