Nature-inspired allomelanin nanomedicine alleviates cardiac ischemia/reperfusion injury via scavenging free radicals and ameliorating myocardial microenvironment

Myocardial ischemia/reperfusion (I/R) injury is the resultantly pathological heart damage from the restoration of blood supply through percutaneous coronary intervention. Herein, inspired by naturally occurring antioxidative allomelanin derived from Fungi, a distinct self-assembly synthesis strategy is ingeniously leveraged to engineer allomelanin nanoparticles (AMNPs) for improving therapeutic efficacy of myocardial I/R injury. These PEGylated [email protected] nanomedicines feature favorable capability in scavenging intracellular free radicals, inhibiting mitochondrial membrane potential depolarization, and improving cell survival. Attributing to the augmented vascular permeability during myocardial I/R injury, [email protected] could target and accumulate at the damaged cardiac sites for photoacoustic visualization. Importantly, [email protected] could achieve the macrophage polarization from M1 to M2 subtype and inhibit neutrophil recruitment, accompanied by the reduced expression of pro-inflammatory genes and the elevated expression of anti-inflammatory genes, respectively, which lead to a considerable reduction in myocardial infarction size and an obvious improvement in cardiac function after I/R injury. This study elucidates that the engineered AMNPs nanomedicines could not only be used as an antioxidative and anti-inflammatory nanoplatform for effective therapy of myocardial I/R injury, but also provide an alternative therapeutic option for other reactive oxygen species-related diseases.