Platelet Membrane and miR-181a-5p Doubly Optimized Nanovesicles Enhance Cardiac Repair Post-Myocardial Infarction through Macrophage Polarization.

Macrophages play a crucial role in cardiac remodeling and prognosis after myocardial infarction (MI). Our previous studies have built a scalable method for preparing scaled stem cell nanovesicles (NVs) and demonstrated their remarkable reparative effects on ischemic heart disease. To further enhance the targeted reparative capabilities of the NVs toward injured myocardium, we employed a dual modification strategy involving platelet membrane coating and miR-181a-5p loading, creating a nanovesicle termed P-181-NV. This study aimed to investigate the efficacy of P-181-NV in targeted reparative interventions for damaged myocardium and to reveal the underlying mechanisms involved. After successful construction and characteristic analysis of P-181-NV, the in vivo tracking techniques demonstrated a significant enhancement in the targeting capacity of P-181-NV toward the injured myocardium. Moreover, P-181-NV showed marked improvements in cardiac function and remodeling as observed through ultrasound echocardiography and Masson's trichrome staining. Furthermore, P-181-NV significantly augmented myocardial cell viability, angiogenic potential, and the polarization ratio of the anti-inflammatory macrophages. The findings of this study underscore the pivotal role of platelet-membrane-coated and miR-181a-5p modified stem cell nanovesicles in facilitating postmyocardial infarction cardiac repair. By modulating macrophage polarization, P-181-NV offers a promising approach for enhancing the efficacy of targeted reparative interventions for damaged myocardium. These results contribute to our understanding of the potential of nanovesicles as therapeutic agents for cardiac repair and regeneration, presenting avenues for future research and clinical applications.