Delivery of therapeutic carbon monoxide by gas-entrapping materials
Name
scitranslmed.abl4135.pdf
Description
Published version
Size
3.11 MB
Format
Adobe PDF
Checksum (MD5)
a14b82403f4bce19740fb207d994dc80
Author(s)
Byrne, James D.
Gallo, David
Boyce, Hannah
Becker, Sarah L.
Kezar, Kristi M.
Cotoia, Alicia T.
Feig, Vivian R.
Lopes, Aaron
Csizmadia, Eva
Longhi, Maria Serena
Date Issued
June 29, 2022
Journal
Science Translational Medicine
Publisher
American Association for the Advancement of Science
Citation
James D. Byrne et al. ,Delivery of therapeutic carbon monoxide by gas-entrapping materials.Sci. Transl. Med.14,eabl4135(2022).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Division of Comparative Medicine
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/scitranslmed.abl4135
