GPx-like phenolic-amine nanoparticles with onion peel-off model for constantly generative anti-inflammation and anti-oxidation capability

Oxidative stress and inflammation are hallmark characteristics of Atherosclerosis (AS) and are crucial points for treatment. Polyphenolic materials have been widely used in anti-inflammatory and antioxidant therapy due to their naturally excellent antioxidant properties, which are limited by the irreversible depletion of a limited number of phenolic hydroxyl groups under oxidative stress. Therefore, polyphenols alone cannot meet the need for long-lasting anti-inflammatory and antioxidant effects in atherosclerosis. In this work, inspired by the natural antioxidant defense system in living organisms, we introduce the CASe nanoparticle capitalizing on the synergistic action of polyphenols and diselenium. In vitro and in vivo experiments have demonstrated that the incorporation of diselenium not only enhance the reactive oxygen species (ROS) scavenging synergized with polyphenols, but also imparts glutathione peroxidase (GPx)-like activity and in situ nitric oxide (NO) -catalyzed release. In addition, ROS-triggered onion peel-off degradation ensures the continuous generation of refreshed surfaces, endowing CASe with a persistent anti-inflammatory and antioxidant capacity. These features facilitate the long-term treatment of chronic inflammatory diseases, providing a dynamic and effective approach for AS treatment.