Engineering extracellular vesicles for targeted therapeutic delivery in the heart

Heart failure is a leading cause of morbidity and mortality, highlighting the need for improved therapeutic strategies. Critical to the success of therapies is efficient and targeted delivery systems. Extracellular vesicle-based delivery systems have emerged as promising candidates due to their biocompatibility and low immunogenicity. While extracellular vesicles from a wide variety of cells have been used, they have demonstrated divergent effects on the heart. The present review first summarizes the current sources of extracellular vesicles employed in heart failure therapy and their contrasting outcomes. The review then examines the view that these contrasting outcomes arise from limited cell specificity, inefficient delivery, and suboptimal cargo loading. Finally, the review discusses how these problems are being dealt with by recent advances, including genetic modification, chemical functionalization, and enhanced loading strategies. Together, these approaches highlight the potential of extracellular vesicle-based systems as precision therapeutics in cardiovascular medicine.