Cell signaling factor nitric oxide (NO) is mainly produced by action of arginine with nitrogen monoxide synthase secreted by endothelial cells (ECs). ECs are the main source of NO in the vascular system. The sustained release of NO is an important factor in maintaining cardiovascular homeostasis and regulating vasodilatation. In addition, NO has been proven to play an important role in preventing thrombosis, inhibiting proliferation and adhesion of smooth muscle cells (SMCs), and inhibiting leukocyte activation. NO also plays an important biological role in the immune response, anti-cancer, anti-bacterial and atherosclerosis treatment. NO also plays an important role in the mobilization, differentiation and function of endothelial progenitor cells (EPCs). Therefore, NO is a potentially ideal molecule for treating cardiovascular diseases, improving the biocompatibility of cardiovascular devices (such as vascular stents, artificial blood vessels, central venous catheters, oxygenators, etc.), designing antimicrobial materials and designing anticancer materials.
In the past 20 years, the research of NO-based clinical treatment mainly focused on developing effective NO-releasing and NO-generating materials. The challenge for NO-releasing materials primarily comprises short half-life of donor for NO production and uncertain safety dose for in vivo NO application, which is a major factor limiting its commercial use. However, long-term NO release is required for the coating of biomedical devices for long-term implantation such as vascular stents and artificial blood vessels, and depletion NO delivery systems are thus not ideal candidates.
There is an endogenous NO donor nitrosothiol (RSNO) in the blood, for example, S-nitrosoglutathione (GSNO), S-nitrosocysteine (CysNO), and S-nitrosoalbumin (AlbSNO). Glutathione peroxidase (GPx) has been found to catalyze the decomposition of RSNO in the presence of thiol in vivo. Organic selenium compounds such as selenocystamine (SeCA) and 3,3′-diselenodipropionic acid (SeDPA), and organic sulfur compounds such as cystamine and cysteine have GPx-like activity to catalyze RSNO decomposition for NO production. Fixing an organic selenium compound or an organic sulfur compound onto the surface of a material is a conventional method for preparing a NO-generating material. However, there are many shortcomings of currently reported NO catalytically active materials. For example, the substance with the GPx-like catalytic activity is usually grafted onto a surface of a material, and the grafting amount depends on the number of functional groups on the surface of the material. However, the surface of most materials lacks functional groups, which leads to insufficient grafting of the GPx-like catalytically active molecules and insufficient catalyzed release of NO. In addition, most of the NO catalytically active materials do not have a strong binding site with the base material to be modified, resulting in poor stability and a shorter NO release cycle.