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