Systematic Review: Engineered Extracellular Vesicles Offer Multi-Modal Therapeutic Potential for Ischemic Heart Diseases

Current treatments for ischemic heart diseases (IHD) often fall short due to the condition's complex pathology, which involves multiple intertwined mechanisms like inflammation, fibrosis, and cell death. Single-target therapies have shown limited efficacy, necessitating approaches that offer multi-targeted synergy, precise delivery, and long-lasting effects. Engineered extracellular vesicles (EVs) have emerged as a promising research area for IHD due to their inherent ability to carry therapeutic signaling molecules, achieve precise tissue targeting, and exhibit excellent biocompatibility, addressing critical gaps in current therapeutic strategies.

This systematic review synthesized findings on engineered extracellular vesicles (EVs) for ischemic heart diseases (IHD). Researchers conducted comprehensive searches across 8 databases, including PubMed, Embase, and Web of Science. Following strict inclusion and exclusion criteria, 50 animal studies were selected for detailed analysis. Two independent researchers meticulously screened the literature, extracted relevant information on EV modification methods, targeting strategies, and multi-pathway therapeutic effects, and evaluated the quality of the included studies to ensure rigor and reliability.

The systematic review of 50 animal studies revealed diverse strategies for engineering EVs to enhance their therapeutic potential in ischemic heart diseases. Modification methods primarily included internal loading/knockdown of therapeutic molecules, surface modification with specific ligands, membrane fusion techniques, combination with biotechnological materials, and pre-treatment of parent cells. To improve targeting, studies utilized targeting peptides or specific antibodies for surface modification, membrane fusion, and direct in situ cardiac delivery, significantly enhancing EV enrichment in ischemic myocardium. > Engineered EVs demonstrated beneficial effects on cardiac function through multiple pathways, including alleviating myocardial-fibrosis, inhibiting inflammatory-responses, promoting angiogenesis, reducing cardiomyocyte-apoptosis, and improving mitochondrial-metabolism. This multi-modal therapeutic approach was conceptualized as a pyramid, with improved cardiac function as the foundation, classical cardioprotective pathways as primary pillars, and metabolic modulation as a crucial supplement.