Gold Nanorod-Based Nanoplatform Catalyzes Constant NO Generation and Protects from Cardiovascular Injury.

Abstract

Cardiovascular disease is a leading cause of death, and one of the effective therapeutic strategies for cardiovascular disease is to provide a controlled, constant supply of nitric oxide (NO) in a mild manner; however, this has proved challenging in the clinic. To address this problem, we built a nitric oxide synthase (NOS)-like nanoplatform (NanoNOS) that consists of a noble metal nanoparticle core and a mesoporous silica shell and demonstrated the ability of NanoNOS to catalyze production of NO <i>in vitro</i>. Mechanistic studies show that the catalysis consists of a three-step reaction: the oxidation of NADPH to produce O₂^-<i>via</i> oxidase-like activity and the subsequent dismutation of O₂^- to H₂O₂<i>via</i> SOD-like activity, followed by H₂O₂-mediated oxidation of l-arginine to produce NO <i>via</i> a nonenzymatic pathway. The generation of NO is precisely regulated by both the content of the NanoNOS species and the plasmon excitation. We found that NanoNOS greatly suppressed injury-driven monocyte-endothelial cell adhesion, suggesting the NanoNOS treatment could help prevent cardiovascular disease. With such a design as well as plasmon excitation that allows for controlled and constant catalytic activity, NanoNOS technology could have a variety of biomedical applications.