Mycophenolic Acid-loaded Naïve Macrophage-derived Extracellular Vesicles Rescue Cardiac Myoblast after Inflammatory Injury

[Image: see text] Exosomes are natural endogenous extracellular vesicles with phospholipid-based bilayer membrane structures. Due to their unique protein-decorated membrane properties, exosomes have been regarded as promising drug carriers to deliver small molecules and genes. A number of approaches have been developed for exosome-based drug loading. However, the drug loading capability of exosomes is inconsistent, and the effects of loading methods on the therapeutic efficacy have not been investigated in detail. Herein, we developed anti-inflammatory drug-loaded exosomes as an immunomodulatory nanoplatform. Naïve macrophage-derived exosomes (Mϕ-EVs) were loaded with the anti-inflammatory drug mycophenolic acid (MPA) by three major loading methods. Loading into exosomes significantly enhanced anti-inflammatory and antioxidation effects of MPA in vitro compared to free drugs. These findings provide a scientific basis for developing naïve macrophage-secreted exosomes as drug carriers for immunotherapy.