Ingestible Artificial Urinary Biomarker Probes for Urine Test of Gastrointestinal Cancer.

Although colorectal cancer diagnosed at early stage shows high curability, methods simultaneously possessing point-of-care testing ability and high sensitivity are limited. Here, we present an orally deliverable biomarker-activatable probe (termed as HATS) for early detection of orthotopic tumor via remote urinalysis. To enable its oral delivery to 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 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-cyclooctene-caged resorufin (TCO-Reso) to afford a rapid and specific fluorescence enhancement of TCO-Reso. Such signal readout is correlated with the urinary tetrazine concentration and thus measures the level of cancer biomarker in colon. HATS-based optical urinalysis detects orthotopic colon tumor two weeks earlier than clinical serological test and can be developed to point-of-care paper test. Thereby, HATS-based urinalysis provides a non-invasive and sensitive approach for cancer screening at low-resource settings. This article is protected by copyright. All rights reserved.