Biomimetic Bone Marrow Monocyte Membrane-Fused Extracellular Vesicles for Targeted Therapy of Myocardial Infarction.

Myocardial infarction (MI) represents a major public health challenge. Extracellular vesicles (EVs) hold considerable promise as therapeutics for cardiovascular disorders. However, the targeted delivery of them to the heart has received relatively limited research. Acute MI is often accompanied by severe inflammation. After MI, numbers of monocytes/macrophages are rapidly mobilized from the circulation and accumulate within the ischemic myocardial tissue. This recruitment is driven by the inflammatory homing signals emanating from the injured cardiac region. In this work, we develop a biomimetic nanovesicle by fusing membranes isolated from bone marrow mononuclear cells (Mon) with extracellular vesicles derived from healthy human plasma (M-hEV). This biomimetic delivery platform achieves site-specific accumulation at damaged vascular endothelial cells and cardiomyocytes by leveraging two key molecular recognition mechanisms: the monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) and intercellular adhesion molecule-1 (ICAM-1)/CD11b axes. The results indicate that M-hEV can inhibit apoptosis of vascular endothelial cells and cardiomyocytes, promote angiogenesis and regulate macrophage polarization at the cellular and animal levels. Furthermore, M-hEV can home to the MI heart, reduce the infarct size, reduce the inflammation level, and improve cardiac function. This biomimetic system provides a novel approach to explore new targeted drugs for MI treatment.