Targeting Strategies of Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases.

Cardiovascular disease (CVD) is a significant cause of cardiac and vascular-related deaths worldwide. While traditional drug and surgical treatments can alleviate symptoms and slow progression, they cannot regenerate heart tissue or reverse function. Heart transplantation, although a radical cure, is limited by donor availability, risks, and costs. Stem cell therapy has gained attention as a potential treatment option, but is hindered by low retention rates post-transplantation. Extracellular vesicles (EVs) are nanoscale membrane vesicles found in various cells and play a key role in the paracrine effects of stem cells. Despite being a promising treatment for cardiovascular diseases, the short plasma half-life and non-specific uptake by the liver and spleen significantly impact its therapeutic efficacy in the heart. This review examines the current understanding of extracellular vesicles and recent advancements in strategies to reduce EV loss and enhance targeted delivery for cardiovascular disease treatment. Approaches such as hydrogel incorporation, vesicular membrane modifications, fusion techniques, and inhibition of monocyte-macrophage system (MPS) clearance are discussed. The paper concludes by addressing the current status of extracellular vesicle therapy and provides insights into its future development.