Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer

Although colorectal cancer diagnosed at an early stage shows high curability, methods simultaneously possessing point-of-care testing ability and high sensitivity are limited. Here, an orally deliverable biomarker-activatable probe (termed as HATS) for early detection of orthotopic tumors via remote...

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Main Authors: Xu, Cheng, Xu, Mengke, Hu, Yuxuan, Liu, Jing, Cheng, Penghui, Zeng, Ziling, Pu, Kanyi
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/174214
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1742142024-03-22T15:31:53Z Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer Xu, Cheng Xu, Mengke Hu, Yuxuan Liu, Jing Cheng, Penghui Zeng, Ziling Pu, Kanyi School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Bioorthogonal reaction Cancer detection Although colorectal cancer diagnosed at an early stage shows high curability, methods simultaneously possessing point-of-care testing ability and high sensitivity are limited. Here, an orally deliverable biomarker-activatable 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-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 biomarkers in the colon. HATS-based optical urinalysis detects orthotopic colon tumors two weeks earlier than clinical serological tests and can be developed to a point-of-care paper test. Thereby, HATS-based urinalysis provides a non-invasive and sensitive approach to cancer screening at low-resource settings. Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version K.P. thanks the Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005), and Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support. 2024-03-21T01:44:34Z 2024-03-21T01:44:34Z 2024 Journal Article Xu, C., Xu, M., Hu, Y., Liu, J., Cheng, P., Zeng, Z. & Pu, K. (2024). Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer. Advanced Materials. https://dx.doi.org/10.1002/adma.202314084 0935-9648 https://hdl.handle.net/10356/174214 10.1002/adma.202314084 38446383 2-s2.0-85187698423 en NRF-NRFI07-2021-0005 MOE-T2EP30220-0010 MOE‐T2EP30221‐0004 Advanced Materials © 2024 Wiley-VCH GmbH. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1002/adma.202314084. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
Bioorthogonal reaction
Cancer detection
spellingShingle Medicine, Health and Life Sciences
Bioorthogonal reaction
Cancer detection
Xu, Cheng
Xu, Mengke
Hu, Yuxuan
Liu, Jing
Cheng, Penghui
Zeng, Ziling
Pu, Kanyi
Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
description Although colorectal cancer diagnosed at an early stage shows high curability, methods simultaneously possessing point-of-care testing ability and high sensitivity are limited. Here, an orally deliverable biomarker-activatable 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-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 biomarkers in the colon. HATS-based optical urinalysis detects orthotopic colon tumors two weeks earlier than clinical serological tests and can be developed to a point-of-care paper test. Thereby, HATS-based urinalysis provides a non-invasive and sensitive approach to cancer screening at low-resource settings.
author2 School of Chemistry, Chemical Engineering and Biotechnology
author_facet School of Chemistry, Chemical Engineering and Biotechnology
Xu, Cheng
Xu, Mengke
Hu, Yuxuan
Liu, Jing
Cheng, Penghui
Zeng, Ziling
Pu, Kanyi
format Article
author Xu, Cheng
Xu, Mengke
Hu, Yuxuan
Liu, Jing
Cheng, Penghui
Zeng, Ziling
Pu, Kanyi
author_sort Xu, Cheng
title Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
title_short Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
title_full Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
title_fullStr Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
title_full_unstemmed Ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
title_sort ingestible artificial urinary biomarker probes for urine test of gastrointestinal cancer
publishDate 2024
url https://hdl.handle.net/10356/174214
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