GEVSod2 Powder: A Modified Product Based on Biovesicles Functioned in Air Pollution PM2.5-Induced Cardiopulmonary Injury

The prevention of air pollution-related cardiopulmonary disorders has been largely overlooked despite its important burden. Extracellular vesicles (EVs) have shown great potential as carriers for drug delivery. However, the efficiency and effect of EVs derived from different sources on ambient fine particulate matter (PM2.5)-induced cardiopulmonary injury remain unknown. Using PM2.5-exposed cellular and mouse models, we investigated the prevention of air pollution-related cardiopulmonary injury via an innovative strategy based on EV delivery. By using a “2-step” method that combines bibliometric and bioinformatic analysis, we identified superoxide dismutase 2 (Sod2) as a potential target for PM2.5-induced injury. Sod2-overexpressing plasmid was constructed and loaded into human plasma-, bovine milk-, and fresh grape-derived EVs, ultimately obtaining modified nanoparticles including PEVSod2, MEVSod2, and GEVSod2, respectively. GEVSod2, especially its lyophilized GEVSod2 powder, exhibited superior protection against PM2.5-induced cardiopulmonary injury as compared to PEVSod2 and MEVSod2. High-sensitivity structured illumination microscopy imaging and immunoblotting showed that GEVSod2 powder treatment altered lysosome positioning by reducing Rab-7 expression. Our findings support the use of fruit-derived EVs as a preferred candidate for nucleic acid delivery and disease treatment, which may facilitate the translation of treatments for cardiopulmonary injuries.