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Delivery of therapeutic carbon monoxide by gas-entrapping materials

2022; American Association for the Advancement of Science; Volume: 14; Issue: 651 Linguagem: Inglês

10.1126/scitranslmed.abl4135

1946-6242

James D. Byrne, David Gallo, Hannah Boyce, Sarah Becker, Kristi M. Kezar, Alicia T. Cotoia, Vivian R. Feig, Aaron Lopes, Eva Csizmadia, Maria Serena Longhi, Jung Seung Lee, Hyunjoon Kim, Adam Wentworth, Sidharth Shankar, Ghee Rye Lee, Jianling Bi, Emily Witt, Keiko Ishida, Alison Hayward, Johannes Kuosmanen, J. A. Jenkins, Jacob Wainer, Aya Aragon, Kaitlyn Wong, Christoph Steiger, William R. Jeck, Dustin E. Bosch, Mitchell C. Coleman, Douglas R. Spitz, Michael S. Tift, Róbert Langer, Leo E. Otterbein, Giovanni Traverso,

Optimism, Hope, and Well-being

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.