A self-assembly nanozyme for repairing myocardial injury via inherent and endogenous antioxidant collaboration with anti-inflammatory and angiogenesis

• A four-in-one nanozyme was constructed by self-assembly. • The nanozyme has super-antioxidant, anti-inflammatory, and pro-vascular functions. • The nanozyme provides a new therapeutic strategy to myocardial infarction injury. Antioxidant therapy is the key to the repair of myocardial infarction injury. The intracellular antioxidant system requires the synergistic action of multiple antioxidant mechanisms. However, the existing antioxidant therapy generally uses a single antioxidant mechanism, which is difficult to meet the needs of injured myocardial repair. In this study, four antioxidant natural drugs, L-arginine (Arg), quercetin (Qc), lipoic acid (LA), and Mn 2+ , were selected to construct a four-in-one Arg-Qc-LA-Mn 2+ nanozyme by self-assembly via supramolecular interaction in one-step in aqueous phase under mild conditions, avoiding the addition of extra carrier materials and their potential side-effects. In this process, the polyphenol groups of Qc spontaneously reacted with Mn 2+ to form a metal-polyphenol network structure. Meanwhile, Arg and LA also self-assembled into the network structure through non-covalent interactions. The so-obtained nanozyme had super-antioxidant activity via collaboration of inherent and endogenous antioxidant mechanisms. In addition, Arg also worked as a pro-vascularizing agent, and Qc also acted as an anti-inflammatory drug. Through cellular and myocardial infarction animal experiments, the nanozyme efficiently scavenged ROS, protected mitochondria, decreased calcium overload, inhibited inflammatory response, promoted vascular neogenesis, reduced injury area, and improved cardiac functions