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However, current methods are unsuitable for routine use because of low accuracy and complexity. In this study, we developed a universal detection platform based on a G\u2010quadruplex@DNA nano\u2010highway network (G4@DNA\u2010NHWN). This platform used aptamer\u2010triggered hybridization chain reaction and streptavidin\u2010biotin crosslinking to construct a protein\u2010scaffolded DNA nanostructure enriched with split G4\n                    <jats:italic>via<\/jats:italic>\n                    a one\u2010pot method at room temperature, enabling sensitive and rapid detection of exosomes. Vimentin, a protein overexpressed in exosomes during the progression and metastasis of breast cancer, was selected as an example. Vimentin binding to the aptamer in G4@DNA\u2010NHWN induces structural disassembly, preventing the split G4 from forming G4\u2010Pb\n                    <jats:sup>2+<\/jats:sup>\n                    complexes with Pb\n                    <jats:sup>2+<\/jats:sup>\n                    , thereby increasing the free Pb\n                    <jats:sup>2+<\/jats:sup>\n                    . Electrochemical (EC) detection enabled the homogeneous quantification of vimentin by directly distinguishing the EC signal differences between the inert G4\u2010Pb\n                    <jats:sup>2+<\/jats:sup>\n                    complex and Pb\n                    <jats:sup>2+<\/jats:sup>\n                    . The results demonstrated that this system achieved exosomes detection with a sensitivity as 30 particles\/mL within 1 h, and exhibited excellent selectivity. Validation across 42 clinical samples demonstrated a concordance rate of &gt;\u00a090% with the clinical diagnoses. As a DNA\u2010functionalized nanomaterial platform, this system holds the promise of approaches in targeted drug delivery and other biomedical applications beyond biosensing.\n                  <\/jats:p>","DOI":"10.1002\/smll.202510625","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:03:59Z","timestamp":1769673839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Programmable G\u2010Quadruplex@DNA Nano\u2010Highway Network Platform Enables One\u2010Pot Electrochemical Detection of Exosomes for Breast Cancer Lymph Node Metastasis Evaluation"],"prefix":"10.1002","volume":"22","author":[{"given":"Binxu","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Med+X Center for Manufacturing Department of General Surgery State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Breast Center West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runlian","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Med+X Center for Manufacturing Department of General Surgery State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Med+X Center for Manufacturing Department of General Surgery State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Breast Center West China Hospital Sichuan 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