Journal article
Delivery of therapeutic carbon monoxide by gas-entrapping materials
Science translational medicine, Vol.14(651), pp.eabl4135-eabl4135
06/29/2022
DOI: 10.1126/scitranslmed.abl4135
PMCID: PMC9576196
PMID: 35767653
Abstract
Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of administration can present clinical challenges. The capacity to deliver CO directly and safely to the gastrointestinal (GI) tract could transform the management of diseases affecting the GI mucosa such as inflammatory bowel disease or radiation injury. To address this unmet need, inspired by molecular gastronomy techniques, we have developed a family of gas-entrapping materials (GEMs) for delivery of CO to the GI tract. We show highly tunable and potent delivery of CO, achieving clinically relevant CO concentrations in vivo in rodent and swine models. To support the potential range of applications of foam GEMs, we evaluated the system in three distinct disease models. We show that a GEM containing CO dose-dependently reduced acetaminophen-induced hepatocellular injury, dampened colitis-associated inflammation and oxidative tissue injury, and mitigated radiation-induced gut epithelial damage in rodents. Collectively, foam GEMs have potential paradigm-shifting implications for the safe therapeutic use of CO across a range of indications.
Details
- Title: Subtitle
- Delivery of therapeutic carbon monoxide by gas-entrapping materials
- Creators
- James D Byrne - Massachusetts Institute of TechnologyDavid Gallo - Beth Israel Deaconess Medical CenterHannah Boyce - Brigham and Women's HospitalSarah L Becker - Brigham and Women's HospitalKristi M Kezar - University of North Carolina WilmingtonAlicia T Cotoia - University of North Carolina WilmingtonVivian R Feig - Brigham and Women's HospitalAaron Lopes - Brigham and Women's HospitalEva Csizmadia - Beth Israel Deaconess Medical CenterMaria Serena Longhi - Beth Israel Deaconess Medical CenterJung Seung Lee - Brigham and Women's HospitalHyunjoon Kim - Brigham and Women's HospitalAdam J Wentworth - Brigham and Women's HospitalSidharth Shankar - Beth Israel Deaconess Medical CenterGhee Rye Lee - Beth Israel Deaconess Medical CenterJianling Bi - University of IowaEmily Witt - University of IowaKeiko Ishida - Brigham and Women's HospitalAlison Hayward - Massachusetts Institute of TechnologyJohannes L P Kuosmanen - Massachusetts Institute of TechnologyJosh Jenkins - Massachusetts Institute of TechnologyJacob Wainer - Brigham and Women's HospitalAya Aragon - Massachusetts Institute of TechnologyKaitlyn Wong - Brigham and Women's HospitalChristoph Steiger - Brigham and Women's HospitalWilliam R Jeck - Duke UniversityDustin E BoschMitchell C Coleman - HoldenDouglas R Spitz - HoldenMichael Tift - University of North Carolina WilmingtonRobert Langer - Massachusetts Institute of TechnologyLeo E Otterbein - Beth Israel Deaconess Medical CenterGiovanni Traverso - Brigham and Women's Hospital
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.14(651), pp.eabl4135-eabl4135
- DOI
- 10.1126/scitranslmed.abl4135
- PMID
- 35767653
- PMCID
- PMC9576196
- NLM abbreviation
- Sci Transl Med
- eISSN
- 1946-6242
- Language
- English
- Date published
- 06/29/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pathology; Orthopedics and Rehabilitation; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984274755602771
Metrics
20 Record Views