Extracellular Vesicle-Based Strategies for the Prevention of Chemotherapy-Induced Cardiotoxicity

Chemotherapy-induced cardiotoxicity (CIC) is a major limitation of modern anticancer therapy, particularly with anthracyclines and targeted agents, and contributes to long-term cardiovascular complications in cancer survivors. Extracellular vesicles (EVs) are nanoscale lipid-bilayer particles that mediate intercellular communication through the transfer of proteins, nucleic acids, and lipids. Emerging evidence indicates that EVs play a dual role in CIC. On one hand, EVs released from tumor cells or stressed cardiomyocytes can propagate cardiotoxic signals by modulating pathways related to oxidative stress, mitochondrial dysfunction, apoptosis, and inflammatory responses. On the other hand, EV-associated molecular cargo, including specific microRNAs and proteins, shows promise as minimally invasive biomarkers for early detection and monitoring of cardiac injury during chemotherapy. In addition, EVs derived from stem or progenitor cells, as well as engineered EVs with modified cargo or surface ligands, have demonstrated cardioprotective potential by attenuating oxidative damage, suppressing apoptosis, and modulating immune and inflammatory signaling in the injured myocardium. Despite these advances, several barriers hinder clinical translation, including vesicle heterogeneity, limited targeting specificity, challenges in standardized isolation and characterization, and insufficient safety and efficacy validation. This review summarizes the mechanistic roles of EVs in the development of CIC, highlights their emerging value as diagnostic biomarkers and therapeutic carriers, and discusses current technical challenges and future directions for translating EV-based strategies into clinical cardio-oncology practice.