In situ growth of nano-antioxidants on cellular vesicles for efficient reactive oxygen species elimination in acute inflammatory diseases

Reactive oxygen species (ROS) are key contributors to inflammatory progression and damage. Upon clinical and experimental observation of vascular abnormalities in acute inflammatory diseases, we explore cellular vesicles as templates and carriers to elevate therapeutic performance of nano-antioxidant. Specifically, we develop a mild one-pot approach for in situ growth of cerium oxide (Ce) nanocrystals onto nano-sized red blood cells vesicles (ReVs). Besides excellent biocompatibility, Ce-ReVs have very high ROS-scavenging activity, which is experimentally and theoretically explained by discovering the unique functions of membrane lipids in optimizing Ce nanocrystals with ultrasmall size (~ 3 nm) and ultrahigh Ce(III) content (~ 60.8%). In colitis and acute liver injury models, Ce-ReVs notably enhance accumulation at the inflamed sites and confer strong ROS elimination. Moreover, we upgrade the system by hybridizing ReVs with mesenchymal stem cell-derived exosomes and demonstrate additional repair function of highly damaged tissues, further verifying the satisfactory flexibility and therapeutic efficacy.