Carbon Monoxide Therapeutics in Biological Systems

Carbon monoxide (CO) has emerged from a reputation as a toxic pollutant to a recognised endogenous gasotransmitter with diverse physiological roles. Enzymatic degradation of haem by heme oxygenase-1 generates low steady-state levels of CO, which modulate vascular tone via soluble guanylate cyclase activation, suppress inflammatory cascades, and protect tissues against oxidative stress and apoptosis. These pleiotropic actions have motivated the design of carbon monoxide-releasing molecules (CORMs) to administer controlled CO doses without the hazards of inhaled gas. Advances in organometallic chemistry, materials science and cellular imaging have enabled the development of targeted delivery platforms—ranging from polysaccharide-conjugated CORMs that home to specific tissues, to light-triggered photoCORMs and porous metal–organic frameworks that permit spatial and temporal control. Through fine-tuning of release kinetics and biocompatibility, CO therapeutics are being explored for protection in ischaemia–reperfusion injury, mitigation of chronic inflammation, regulation of metabolic homeostasis and as adjuncts to antimicrobial strategies. Ongoing challenges include optimisation of pharmacokinetics, rigorous safety profiling and real-time monitoring of CO distribution in vivo. Bridging these gaps will be essential to translate promising preclinical findings into new interventions for cardiovascular, inflammatory and metabolic disorders, as well as to combat antibiotic-resistant infections.

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Carbon Monoxide Therapeutics in Biological Systems publication trend

The graph below shows the total number of articles in carbon monoxide therapeutics in biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Gasotransmitter: Endogenously produced gaseous signalling molecule that diffuses freely across membranes to regulate physiological processes.

Carbon monoxide-releasing molecule (CORM): Organometallic or coordination compound engineered to deliver predetermined amounts of CO under physiological conditions.

PhotoCORM: Light-activated carbon monoxide donor that releases CO upon irradiation at specific wavelengths, enabling spatiotemporal precision.

Glyco-CORM: Polysaccharide-conjugated CORM designed to exploit carbohydrate-mediated targeting and improve tissue-specific accumulation.

Metal–organic framework (MOF): Crystalline porous network of metal nodes and organic linkers used as a scaffold for loading and controlled release of therapeutic agents such as CO.

References

1. Development of carbon monoxide-releasing molecules conjugated to polysaccharides (glyco-CORMs) for delivering CO during obesity. Pharmacological Research (2023).
2. Carbon monoxide – physiology, detection and controlled release. Chemical Communications (2014).
3. Light responsive metal–organic frameworks as controllable CO-releasing cell culture substrates. Chemical Science (2017).
4. Reactive Oxygen Species Mediate Bactericidal Killing Elicited by Carbon Monoxide-releasing Molecules*. Journal of Biological Chemistry (2011).
5. CO-releasing Metal Carbonyl Compounds as Antimicrobial Agents in the Post-antibiotic Era*. Journal of Biological Chemistry (2015).
6. Carbon Monoxide-releasing Antibacterial Molecules Target Respiration and Global Transcriptional Regulators*. Journal of Biological Chemistry (2008).
7. Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs). Medical Gas Research (2012).
8. Visible Light-Activated PhotoCORMs. Inorganics (2017).
9. Carbon monoxide and mitochondria—modulation of cell metabolism, redox response and cell death. Frontiers in Physiology (2015).