| Title: | Engineering synthetic breath biomarkers for respiratory disease |
| Author(s): | Chan LW; Anahtar MN; Ong TH; Hern KE; Kunz RR; Bhatia SN; |
| Address: | "Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. Biological and Chemical Technologies Group, Massachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. sbhatia@mit.edu. Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. sbhatia@mit.edu. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA. sbhatia@mit.edu. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. sbhatia@mit.edu. Broad Institute, Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. sbhatia@mit.edu. Howard Hughes Medical Institute, Cambridge, MA, USA. sbhatia@mit.edu" |
| DOI: | 10.1038/s41565-020-0723-4 |
| ISSN/ISBN: | 1748-3395 (Electronic) 1748-3387 (Print) 1748-3387 (Linking) |
| 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" |
| Keywords: | "Animals Biomarkers/*analysis Breath Tests/instrumentation/*methods Computer Simulation Dose-Response Relationship, Drug Drug Carriers/administration & dosage/chemistry Female Glycine/analogs & derivatives/pharmacology Humans Leukocyte Elastase/antagonists;" |
| Notes: | "MedlineChan, Leslie W Anahtar, Melodi N Ong, Ta-Hsuan Hern, Kelsey E Kunz, Roderick R Bhatia, Sangeeta N eng HHMI/Howard Hughes Medical Institute/ K99 EB028311/EB/NIBIB NIH HHS/ R00 EB028311/EB/NIBIB NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2020/07/22 Nat Nanotechnol. 2020 Sep; 15(9):792-800. doi: 10.1038/s41565-020-0723-4. Epub 2020 Jul 20" |
