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A Peptide-Based Material for Therapeutic Carbon Monoxide Delivery.

ABSTRACT: We report on the preparation of the first material for therapeutic delivery of CO. A peptide amphiphile was synthesized with a covalently attached ruthenium tricarbonyl. Self-assembled nanofiber gels containing this peptide spontaneously released CO with prolonged release kinetics compared to soluble CO donors. Oxidatively stressed cardiomyocytes had improved viability when treated with this peptide, demonstrating its potential as a biodegradable gel for localized therapeutic CO delivery.

SUBMITTER: Matson JB

PROVIDER: S-EPMC3374652 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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A Peptide-Based Material for Therapeutic Carbon Monoxide Delivery.

Matson John B JB Webber Matthew J MJ Tamboli Vibha K VK Weber Benjamin B Stupp Samuel I SI

Soft matter 20120101 25

We report on the preparation of the first material for therapeutic delivery of CO. A peptide amphiphile was synthesized with a covalently attached ruthenium tricarbonyl. Self-assembled nanofiber gels containing this peptide spontaneously released CO with prolonged release kinetics compared to soluble CO donors. Oxidatively stressed cardiomyocytes had improved viability when treated with this peptide, demonstrating its potential as a biodegradable gel for localized therapeutic CO delivery. ...[more]

PMID: 22707978

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Project description:Carbon monoxide (CO) is not only known as a toxic gas due to its characteristics as an odorless molecule and its rapid binding to haem-containing molecules, thus inhibiting the respiratory chain in cells resulting in hypoxia. For decades, scientists established evidence about its endogenously production in the breakdown of haem via haem-oxygenase (HO-1) and its physiological effects. Among these, the modulation of various systems inside the body are well described (e.g., anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-proliferative). Carbon monoxide is able to modulate several extra- and intra-cellular signaling molecules leading to differentiated response according to the specific stimulus. With our growing understanding in the way CO exerts its effects, especially in the mitochondria and its intracellular pathways, it is tempting to speculate about a clinical application of this substance. Since HO-1 is not easy to induce, research focused on the application of the gaseous molecule CO by itself or the implementation of carbon monoxide releasing molecules (CO-RM) to deliver the molecule at a time- and dose dependently safe way to any target organ. After years of research in cellular systems and animal models, summing up data about safety issues as well as possible target to treat in various diseases, the first feasibility trials in humans were established. Up-to-date, safety issues have been cleared for low-dose carbon monoxide inhalation (up to 500 ppm), while there is no clinical data regarding the injection or intake of any kind of CO-RM so far. Current models of human research include sepsis, acute lung injury, and acute respiratory distress syndrome as well as acute kidney injury. Carbon monoxide is a most promising candidate in terms of a therapeutic agent to improve outbalanced organ conditions. In this paper, we summarized the current understanding of carbon monoxide's biology and its possible organ targets to treating the critically ill patients in tomorrow's ICU.

Dataset Information

A Peptide-Based Material for Therapeutic Carbon Monoxide Delivery.

Publications

A Peptide-Based Material for Therapeutic Carbon Monoxide Delivery.

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