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We present a DNA\u2010regulated catalytic\u2010plasmonic colocalization\u2010based synergy coupling mechanism that resolved the spatiotemporal disjunction commonly present in conventional SERS\u2010catalysis systems through programmed spatial confinement. Rolling circle amplification\u2010derived DNA nanocages were employed as programmable spatial regulators to precisely position Au@Pt nanozymes within plasmonic hotspots via base pair encoded hybridization, thereby enforcing spatial and temporal consistency between catalytic generation of Raman\u2010active species and electromagnetic field enhancement. This strategy integrated coordinated interface, pore, and interlayer confinement, enabling cross\u2010scale signal amplification from molecular to microscale levels. As a result, it yielded exceptional SERS enhancement (an approximate 41\u2010fold versus controls), sensitivity (10\n                    <jats:sup>2<\/jats:sup>\n                    exosomes \u00b5L\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), and reproducibility (6.5% RSD). To translate this mechanism into practical application, a portable dual\u2010modal detection platform with potential point\u2010of\u2010care applicability was developed that preserved catalytic\u2010plasmonic colocalization during both colorimetric screening and SERS quantification. The device achieved radical miniaturization (95% volume, 91% weight reduction) and cost\u2010efficiency (90% reduction vs. commercial systems). By coupling programmable nanomaterial design with customizable device engineering, we established a robust paradigm for next\u2010generation POCT, providing a promising platform for biomedical detection, environmental surveillance, and food safety monitoring.\n                  <\/jats:p>","DOI":"10.1002\/adma.74043","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:49:01Z","timestamp":1783410541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA\u2010Regulated Catalytic\u2010Plasmonic Colocalization Enables Synergistic Signal Amplification in SERS and Nanozyme\u2010Based Sensors"],"prefix":"10.1002","volume":"38","author":[{"given":"Yeru","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemical Safety College of Control Science and Engineering China University of Petroleum (East China)  Qingdao 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