From targeted delivery to inflammation suppression: engineering plant exosomes for heart failure therapy post-infarction

Plant-derived exosomes are natural nanovesicles rich in bioactive compounds and show promise for tissue regeneration. However, their clinical use is limited by poor stability and low targeting accuracy. To overcome these issues, we developed an engineered approach to enhance the targeted delivery of plant exosomes, focusing on chronic inflammation-a key driver of heart failure-evaluating their therapeutic potential in myocardial infarction. By optimizing isolation methods and fusing exosomes with synthetic liposomes, we created collagen-targeted hybrid nanovesicles (GEP-NPs). In a mouse model of myocardial infarction, GEP-NPs efficiently accumulated in damaged heart tissue. Compared to non-engineered vesicles, GEP-NPs more effectively reduced fibrosis, suppressed ventricular remodeling, and modulated chronic post-infarction inflammation, thereby preventing progression from acute injury to chronic heart failure. Mechanistic studies showed that GEP-NPs may inhibit the overactive PI3K-AKT-mTOR pathway, which regulates inflammation, cell survival, and metabolism. The bioactive components from plant exosomes likely act effectively within the engineered vesicles to suppress this pathway, reducing persistent inflammation and promoting tissue repair. This work provides a scalable, reproducible method for engineering plant exosomes, improving both delivery precision and stability, and offering a promising strategy for treating chronic cardiac inflammation and preventing heart failure.