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Lateral flow immunoassays (LFAs) enable large\u2010scale screening but lack intrinsic signal amplification. Although nanozymes can enhance LFA readouts, their amplification remains constrained by inefficient hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) activation. Herein, an electronically coupled Au\/PtIr trimetallic nanozyme (Au\/PtIr NPs) is constructed by decorating Au nanoparticle (Au NP) surfaces with island\u2010like PtIr alloy nanodomains. This architecture forms spatially adjacent dual\u2010site adsorption interfaces with heterogeneous electronic properties. Alloy\u2010induced interfacial electronic modulation synergistically optimizes H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    adsorption and facilitates its homolytic O\u2500O bond, selectively enhancing \u2022OH generation and accelerating peroxidase\u2010like (POD\u2010like) catalytic kinetics. Integrated into an LFA platform, Au\/PtIr NPs enable sensitive and reliable detection of \u03b1\u2010fetoprotein (AFP) in clinical samples, with a linear response from 0.2\u20131000 ng mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    and a limit of detection (LOD) of 57.7 pg mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    , which is 390\u2010fold lower than that of conventional Au NP\u2010based 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\u2010of\u2010care detection. This electronic\u2010interface engineering approach provides a generalizable route to catalytic signal amplification for LFA\u2010based diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/smll.74812","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:28:15Z","timestamp":1784802495000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Signal\u2010Amplified Point\u2010of\u2010Care Screening of Hepatocellular Carcinoma Enabled by an Electronically Coupled Au\/PtIr Trimetallic Nanozyme"],"prefix":"10.1002","volume":"22","author":[{"given":"Nana","family":"Song","sequence":"first","affiliation":[{"name":"Shandong Key Laboratory of Analytical Chemistry for Life Science and Intelligent Detection College of Biological Engineering Qingdao University of Science and Technology  Qingdao 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