Cytotoxicity of metal-containing carbon monoxide-releasing molecules: A current assessment

Carbon monoxide-releasing molecules (CORMs) have drawn attention since the beginning of the century. Since then, many publications have been devoted to optimizing the physicochemical properties of CORMs, with a focus on the release kinetics of CO as a function of external stimuli such as light, enzyme, and redox triggering, as well as ligand exchange and pH changes. This was followed by studies on the use of CORMs and later carbon monoxide-releasing nanomaterials (CORNMs) as pharmaceutical active compounds/materials in biological systems. In this context, there is an ongoing debate as to whether the pharmacological efficacy can be clearly attributed to CO alone or whether CO-free metal fragments or both mechanisms contribute to biological efficacy. This review focuses in particular on CORMs and CORNMs that exhibit cell toxicity and on corresponding characterization methods that allow biological efficacy to be assigned. The methods to be used to obtain reliable information on biodistribution and pharmacokinetic properties, as well as the characterization of the kinetics of controlled CO release in living organisms, are outlined.