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Here, an orally deliverable biomarker\u2010activatable probe (termed as HATS) for early detection of orthotopic tumors via remote urinalysis is presented. To enable its oral delivery to the colon, HATS is designed to have remarkable resistance to acidity and digestive enzymes in the stomach and small intestine and negligible intestinal absorption. Upon reaction with a cancer biomarker in the colon segment, HATS releases a small fragment of tetrazine that can transverse the intestinal barrier, enter blood circulation, and ultimately undergo renal clearance to urine. Subsequently, the urinary tetrazine fragment is detected by bioorthogonal reaction with trans\u2010cyclooctene\u2010caged resorufin (TCO\u2010Reso) to afford a rapid and specific fluorescence enhancement of TCO\u2010Reso. Such signal readout is correlated with the urinary tetrazine concentration and thus measures the level of cancer biomarkers in the colon. HATS\u2010based optical urinalysis detects orthotopic colon tumors two weeks earlier than clinical serological tests and can be developed to a point\u2010of\u2010care paper test. Thereby, HATS\u2010based urinalysis provides a non\u2010invasive and sensitive approach to cancer screening at low\u2010resource settings.<\/jats:p>","DOI":"10.1002\/adma.202314084","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T10:59:36Z","timestamp":1709722776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Ingestible Artificial Urinary Biomarker Probes for Urine Test of Gastrointestinal Cancer"],"prefix":"10.1002","volume":"36","author":[{"given":"Cheng","family":"Xu","sequence":"first","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  70 Nanyang Drive Singapore 637457 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  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