Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

Abstract

Carbon monoxide (CO) therapy has emerged as a hot topic under exploration in the field of gas therapy as it shows the promise of treating various diseases. Due to the gaseous property and the high affinity for human hemoglobin, the main challenges of administrating medicinal CO are the lack of target selectivity as well as the toxic profile at relatively high concentrations. Although abundant CO releasing molecules (CORMs) with the capacity to deliver CO in biological systems have been developed, several disadvantages related to CORMs, including random diffusion, poor solubility, potential toxicity, and lack of on‐demand CO release in deep tissue, still confine their practical use. Recently, the advent of versatile nanomedicine has provided a promising chance for improving the properties of naked CORMs and simultaneously realizing the therapeutic applications of CO. This review presents a brief summarization of the emerging delivery strategies of CO based on nanomaterials for therapeutic application. First, an introduction covering the therapeutic roles of CO and several frequently used CORMs is provided. Then, recent advancements in the synthesis and application of versatile CO releasing nanomaterials are elaborated. Finally, the current challenges and future directions of these important delivery strategies are proposed.

One‐Pot Intercalation Strategy for the Encapsulation of a CO‐Releasing Organometallic Molecule in a Layered Double Hydroxide

“…[5] CO has tremendous therapeutic potential in ailments such as rheumatoid arthritis, gastric ulcers, sepsis, lung injury, cardiovascular disease, stroke, transplant rejection, and cancer. [6][7][8] Major drawbacks of CO delivery by inhalation as a gas include lack of tissue specificity, requirement to be performed in a hospital setting, and high dependence of the outcome on the respiratory function of the patient. [5] Solid or liquid dosage of CO has been investigated since 2002 by the development of CO-releasing molecules (CORMs).…”

“…[5] Solid or liquid dosage of CO has been investigated since 2002 by the development of CO-releasing molecules (CORMs). [6][7][8][9][10] Most CORMs developed to date are organometallic carbonyl complexes with CO bound to a transition metal in a low oxidation state, e.g. [Ru(CO) 3 Cl(glycinate)] (CORM-3).…”

“…[11] Multiple studies with such compounds have confirmed the beneficial effects of CO in different animal models of diseases. [7][8][9] CO release from CORMs may be triggered hydrolytically, by ligand substitution, photoactivation (socalled photoCORMs), changes in pH, exposure to reactive oxygen species (ROS), and enzymatic hydrolysis. [8,[12][13][14] However, in many instances the direct delivery of molecular CORMs is likely to be inefficient and may suffer from problems such as enzymatic degradation, poor bioavailability, poor circulation stabil-and controlled release of CO, with two key benefits being the prevention of the premature interaction of the CORM with the biological environment, and the retention of potentially toxic decarbonylation fragments.…”

“…Fortunately, these innate immune defenses may be enhanced by administration of exogenous CO and this has been explored in multiple clinical trials that use gas inhalation as the delivery method . CO has tremendous therapeutic potential in ailments such as rheumatoid arthritis, gastric ulcers, sepsis, lung injury, cardiovascular disease, stroke, transplant rejection, and cancer …”

“…Major drawbacks of CO delivery by inhalation as a gas include lack of tissue specificity, requirement to be performed in a hospital setting, and high dependence of the outcome on the respiratory function of the patient . Solid or liquid dosage of CO has been investigated since 2002 by the development of CO‐releasing molecules (CORMs) . Most CORMs developed to date are organometallic carbonyl complexes with CO bound to a transition metal in a low oxidation state, e.g.…”