pEV-TK-SS31

pEV-TK-SS31 is an engineered, exosome-based, ROS-responsive nanomedicine platform developed for the treatment of acute kidney injury (AKI). It consists of primed extracellular vesicles (pEVs) derived from mesenchymal stem cells (MSCs) that have been 'educated' via exposure to inflammatory cytokines. This inflammatory education upregulates the membrane protein integrin α4β1 on the pEVs, enabling them to target and bind to the adhesion ligand VCAM-1 in the inflammatory environment of injured kidneys. The pEVs are further engineered by conjugating the mitochondria-targeted antioxidant peptide SS31 (elamipretide) via a reactive oxygen species (ROS)-responsive thioketal (TK) linker. Upon reaching the injured kidney, local high levels of ROS trigger the cleavage of the thioketal linker, releasing SS31 to exert mitochondria-targeted antioxidation and mitochondrial protection. Simultaneously, the pEVs deliver anti-inflammatory miRNAs that suppress IRAK1/TRAF6 signaling, thereby synergistically disrupting the inflammation-oxidative stress cycle.