Multivalent Amine Functionalized Carbon Dots Catalyze Efficient Denitrosylation

Abstract Nitric oxide (NO) is an essential signaling molecule with several biological functions and holds great promise in biomedical applications. However, NO delivery strategies have been challenged with its inherent short half‐life and limited transport distance in human tissues. Strategies focused on the catalytic production of NO at the target site would afford an effective biomaterial. Herein, we introduce a carbon dot (CD) platform featuring multivalent amine groups that catalyze the denitrosylation from S ‐nitrosothiols. In the present study, we have developed a novel multivalent amine functionalized carbon dots to catalytically transform endogenous prodrugs S ‐nitrosothiols to generate NO at physiological conditions. The mechanism of NO generation follows a nucleophilic attack of the surface primary amine groups on the electrophilic thiol group of S ‐nitrosothiols, which is supported by various control studies and electron paramagnetic resonance (EPR). Notably, the release of NO is easily tuned by the prodrug concentration and surface density of amines on the CDs. Significantly, the NO‐releasing feature of CDs is integrated with the prototissue module to evaluate the NO release profile in the biological environment. This study will deepen our understanding of designing useful multivalent systems to generate NO from endogenous prodrugs to realize their therapeutic potential.