Neutrophil-derived apoptotic body membranes-fused exosomes targeting treatment for myocardial infarction.

Abstract

Myocardial infarction (MI) poses a substantial threat to human health, prompting extensive research into effective treatment modalities. Preclinical studies have demonstrated the therapeutic potential of mesenchymal stem cell-derived exosomes for cardiac repair. Despite their promise, the inherent limitations of natural exosomes, mainly their restricted targeting capabilities, present formidable barriers to clinical transformation. To address this, it is proposed to enhance their targeting specificity and retention in infarcted myocardium by fusing exosomes with neutrophil-derived apoptotic body membranes (NAM). These NAM inherit the surface signals from neutrophils, which allow them to home in on the damaged tissues and participate in regulating inflammatory responses. In this current work, we utilized a membrane fusion technique to create NAM-fused exosomes (NAM-Exo) for MI treatment. Compared to their native counterparts, NAM-Exo demonstrated enhanced adhesion to inflammatory endothelial cells, replicating the neutrophil recruitment mechanism at sites of myocardial injury in MI. Furthermore, our findings revealed that NAM-Exo not only significantly modulated inflammation responses but also promoted angiogenesis in a mouse model of MI, ultimately leading to improved cardiac function and ventricular remodeling post-treatment. These results underscore the potential of membrane fusion as an effective strategy to enhance the therapeutic efficacy of exosome-based cardiac repair and regeneration therapies, thereby paving the way for their translation into clinical practice.