Theranostic Trigger‐Responsive Carbon Monoxide‐Generating Microbubbles

Abstract

Carbon monoxide (CO) is a gaseous signaling molecule that modulates inflammation, cell survival, and recovery after myocardial infarction. However, handling and dosing of CO as a compressed gas are difficult. Here, light‐triggerable and magnetic resonance imaging (MRI)‐detectable CO release from dimanganese decacarbonyl (CORM‐1) are demonstrated, and the development of CORM‐1‐loaded polymeric microbubbles (COMB) is described as an ultrasound (US)‐ and MRI‐imageable drug delivery platform for triggerable and targeted CO therapy. COMB are synthesized via a straightforward one‐step loading protocol, present a narrow size distribution peaking at 2 µm, and show excellent performance as a CORM‐1 carrier and US contrast agent. Light irradiation of COMB induces local production and release of CO, as well as enhanced longitudinal and transversal relaxation rates, enabling MRI monitoring of CO delivery. Proof‐of‐concept studies for COMB‐enabled light‐triggered CO release show saturation of hemoglobin with CO in human blood, anti‐inflammatory differentiation of macrophages, reduction of hypoxia‐induced reactive oxygen species (ROS) production, and inhibition of ischemia‐induced apoptosis in endothelial cells and cardiomyocytes. These findings indicate that CO‐generating MB are interesting theranostic tools for attenuating hypoxia‐associated and ROS‐mediated cell and tissue damage in cardiovascular disease.

Application of nanotechnology in the treatment of glomerulonephritis: current status and future perspectives

“…H 2 S has a role in neuroprotection and vascular smooth muscle relaxation [ 145 ]. Carbon monoxide-releasing molecules (CORM), as a prodrug producing carbon monoxide, can release CO to play an anti-inflammatory and cytoprotective role [ 146 ]. GSM has the advantage of reducing systemic side effects through local delivery, resulting in the development of stimulus-responsive nanocarriers [ 143 ].…”

Ultrasound-responsive matters for biomedical applications

“…Our study provided new ideas for the preparation of US-responsive microbubbles and a way for US-controlled drug release and delivery of gaseous signaling molecules. Moreover, in addition to H 2 S, numerous gaseous signaling molecules have been carried by microbubbles and exerted biological effects to achieve therapeutic purposes, such as nitric oxide (NO), 83 , 84 , 85 carbon monoxide, 86 , 87 , 88 etc. For example, Liao’s group proposed NO-loaded C4d-targeted microbubbles to successfully treat rats with acute antibody-mediated cardiac allograft rejection due to the immunosuppressive and antithrombotic effects of high NO levels.…”

A CO-mediated photothermal therapy to kill drug-resistant bacteria and minimize thermal injury for infected diabetic wound healing

“…23 The NIR irradiation and increasing temperature will break up the metal-carbonyl complexation. 35 According to the heat balance equation (described in detail in the Experimental section) in a previous report, 26 the temperature of the NPs can reach over 500 °C under a NIR laser irradiation of 1.8 W cm −2 . Such a high temperature enabled an NIR-triggered CO release from CO@mPDA.…”