A nanosystem manipulates angiocrine signaling for cardioprotection in male mice by relocalizing endothelial exosomes

Acting as frontline sensors during cardiovascular injury, endothelial cells respond to acute ischemia by releasing exosomes as angiocrine signals for intercellular communication and cardioprotection. However, these endogenous signals are poorly utilized because released exosomes distribute systemically and show limited exposure in injured myocardium. Here we develop a systemically administered nanosystem for relocalizing circulating endothelial exosomes towards the myocardium, increasing their local availability. The nanosystem captures circulating endothelial exosomes, mediates their transvascular relocalization and promotes delivery to cardiomyocytes in the ischemic myocardium, thereby enhancing the local availability of native angiocrine signals. In a murine model of acute cardiac ischemia using male mice, this strategy increases endothelial exosome exposure in myocardium, improves cardiomyocyte survival, and preserves cardiac function. This approach enhances the reception of native angiocrine signals at the injured myocardium, therefore converting the originally diffuse, short-lived response into a sustained, organ-specific therapeutic exposure. Acute myocardial ischemia induces the release of endothelial exosomes with cardioprotective effect. Here, the authors show that a nanosystem relocalizes circulating endothelial exosomes to ischemic myocardium, increasing local exposure and preserving cardiac function