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Here, we develop a targeted, tandem\u2010activated artificial urinary biomarker sensor (TADEI) for real\u2010time optical imaging and urinalysis of early biomarkers associated with TAAD. After identifying biomarkers from patient tissue samples, TADEI was designed with three key components conjugated to a near\u2010infrared fluorophore: a VCAM\u20101\u2013targeting moiety (overexpressed on inflamed endothelial cells), tandem\u2010responsive substrates for caspase\u20101 (an inflammation mediator) and legumain (a protease relevant to vascular remodeling), and a renal\u2010clearance\u2013enabling moiety. TADEI specifically targets TAAD lesions and activates its fluorescence upon reaction with these early biomarkers after systemic administration. Meanwhile, TADEI is excreted into urine via renal clearance (\u224876%), converting TAAD biomarker levels into urinary signals for optical urinalysis. In a mouse model, a TADEI\u2010based urine test detected TAAD at least 12 days earlier than ultrasound imaging and 16 days earlier than plasma D\u2010dimer assays. The correlation between the urinary signal of activated TADEI and disease severity guided intervention that effectively inhibited TAAD progression, achieving 100% survival compared with 73% for ultrasound\u2010guided therapy and 40% without treatment.<\/jats:p>","DOI":"10.1002\/adma.74390","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:35:52Z","timestamp":1785602152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Targeted, Tandem\u2010Activated Artificial Urinary Biomarker Sensor for Early Detection and Therapeutic Intervention of Thoracic Aortic Aneurysm and Dissection"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-5307","authenticated-orcid":false,"given":"Jie","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Guangdong Provincial Key Laboratory of Precision Medical Diagnostics Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"State Key Laboratory of Multi\u2010organ\u00a0Injury Prevention and Treatment Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Guangdong Provincial Clinical Research Center For Laboratory Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zien","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Biomedical Engineering Technology Research Center For Cardiovascular Disease Department of Cardiology and Laboratory of Heart Center Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"National Engineering Research Centre for Nanomedicine College of Life Science and Technology Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4762-5547","authenticated-orcid":false,"given":"Penghui","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siman","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Guangdong Provincial Key Laboratory of Precision Medical Diagnostics Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"State Key Laboratory of Multi\u2010organ\u00a0Injury Prevention and Treatment Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Guangdong Provincial Clinical Research Center For Laboratory Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Guangdong Provincial Key Laboratory of Precision Medical Diagnostics Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"State Key Laboratory of Multi\u2010organ\u00a0Injury Prevention and Treatment Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Guangdong Provincial Clinical Research Center For Laboratory Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Biomedical Engineering Technology Research Center For Cardiovascular Disease Department of Cardiology and Laboratory of Heart Center Zhujiang Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Cardiovascular Surgery Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-5552","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Centre for Nanomedicine College of Life Science and Technology Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-4750","authenticated-orcid":false,"given":"Yanbin","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Biomedical Engineering Technology Research Center For Cardiovascular Disease Department of Cardiology and Laboratory of Heart Center Zhujiang Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Cardiovascular Surgery Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-8780","authenticated-orcid":false,"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Guangdong Provincial Key Laboratory of Precision Medical Diagnostics Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles Nanfang Hospital Southern Medical University  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