Engineering synthetic breath biomarkers for respiratory disease.

Nature Nanotechnology
Leslie W ChanSangeeta N Bhatia

Abstract

Human breath contains many volatile metabolites. However, few breath tests are currently used in the clinic to monitor disease due to bottlenecks in biomarker identification. Here we engineered breath biomarkers for respiratory disease by local delivery of protease-sensing nanoparticles to the lungs. The nanosensors shed volatile reporters upon cleavage by neutrophil elastase, an inflammation-associated protease with elevated activity in lung diseases such as bacterial infection and alpha-1 antitrypsin deficiency. After intrapulmonary delivery into mouse models with acute lung inflammation, the volatile reporters are released and expelled in breath at levels detectable by mass spectrometry. These breath signals can identify diseased mice with high sensitivity as early as 10 min after nanosensor administration. Using these nanosensors, we performed serial breath tests to monitor dynamic changes in neutrophil elastase activity during lung infection and to assess the efficacy of a protease inhibitor therapy targeting neutrophil elastase for the treatment of alpha-1 antitrypsin deficiency.

References

May 1, 1992·Toxicology and Industrial Health·K KrishnanM E Andersen
Mar 15, 1989·Toxicology and Applied Pharmacology·M L GargasM E Andersen
Feb 8, 2005·American Journal of Respiratory and Critical Care Medicine·Clifford C TaggartNoel G McElvaney
Mar 3, 2005·Lung·Amelia W NgThomas A Heming
Aug 23, 2005·Proceedings of the American Thoracic Society·John S PattonJeffry G Weers
Oct 21, 2005·The New England Journal of Medicine·Gordon D RubenfeldLeonard D Hudson
Jun 27, 2006·Nature Reviews. Immunology·Christine T N Pham
Oct 16, 2007·Journal of Toxicology and Environmental Health. Part a·A NongK Krishnan
Jun 28, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Micaela B ReddyMelvin E Andersen
May 2, 2009·Journal of Pharmaceutical Sciences·Hema GursahaniC Simone Fishburn
Jul 9, 2009·Analytical Chemistry·Alexandre A ShvartsburgBilly Boyle
Jan 19, 2010·Nature Medicine·A McGarry HoughtonSteven D Shapiro
Jul 1, 2011·The New England Journal of Medicine·UNKNOWN National Lung Screening Trial Research TeamJoRean D Sicks
Jul 19, 2011·Helicobacter·António Mário SantosAntónio Sousa Guerreiro
Aug 24, 2011·Journal of Neurogastroenterology and Motility·Uday C Ghoshal
Dec 18, 2012·Nature Biotechnology·Gabriel A KwongSangeeta N Bhatia
Aug 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Danny JonigkSabina Janciauskiene
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Paulina KasperkiewiczMarcin Drag
Jul 12, 2014·Annual Review of Analytical Chemistry·Anton AmannTerence Risby
Jan 9, 2015·Clinical Microbiology Reviews·Jean-Christophe LagierDidier Raoult
Jun 15, 2016·Respiratory Medicine·Susanne I FuchsMonika Gappa
Jul 28, 2016·Pediatric Allergy, Immunology, and Pulmonology·Hengameh H RaissyH William Kelly
Jan 27, 2017·International Journal of Environmental Research and Public Health·Aurélie PelfrêneFrancis Douay
Apr 27, 2017·Chest·Eva PolverinoAntoni Torres
Jun 10, 2017·Analytical Chemistry·Ta-Hsuan OngRoderick Kunz
Jun 6, 2016·Chronic Obstructive Pulmonary Diseases : Journal of the COPD Foundation·Robert A SandhausJeffrey Teckman
Oct 4, 2017·Nature Biomedical Engineering·Ester J KwonSangeeta N Bhatia
Jan 3, 2018·Journal of Breath Research·Pouline M van OortLieuwe D Bos
Feb 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Florie BorelChristian Mueller
Aug 22, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jaideep S DudaniSangeeta N Bhatia
Apr 10, 2019·American Journal of Respiratory and Critical Care Medicine·Michael A CamposRobert A Stockley
Apr 10, 2019·Journal of Breath Research·Edoardo GaudeMarc P van der Schee
May 17, 2019·Journal of Breath Research·William R Bishai, Graham S Timmins
Sep 4, 2019·Nature Nanotechnology·Colleen N LoynachanMolly M Stevens
Sep 14, 2019·Angewandte Chemie·Justin LangePauline Poinot
Sep 19, 2019·Scientific Reports·Bethany M AndersonLaura E Edgington-Mitchell
Apr 3, 2020·Science Translational Medicine·Jesse D KirkpatrickSangeeta N Bhatia

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Citations

Dec 21, 2020·Current Opinion in Pharmacology·Mohammad DoroudianSeamas C Donnelly
Jun 29, 2021·Current Opinion in Biomedical Engineering·Leslie W Chan
Sep 8, 2021·Nature Reviews. Cancer·Gabriel A KwongSangeeta N Bhatia

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Methods Mentioned

BETA
Transmission
gene knockout
ELISA

Software Mentioned

GraphPad Prism

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