Exosome coated with Prussian blue mediated microglial polarization for spinal cord injury

• EXO/PB targets inflammatory macrophages. • Removal of ROS decreases SCI-associated mitochondrial dysfunction. • After targeting inflammatory macrophages, EXO/PB promotes the polarization of microglia M1 to M2. The surge in reactive oxygen species (ROS) and inflammation after acute spinal cord injury (SCI) is a key factor in making this injury irreversible. How to intervene effectively is the basis of therapeutic strategy design. In our study, we explored the potential of Prussian blue nanase, which has catalase and superoxide dismutase-like activity. However, given their high immunogenicity, we chose to leverage the low immunogenicity and biosafety of exosomes to enhance the delivery of these nanase. Recognizing the prevalence of M1 microglia in local inflammation, we used exosomes derived from bone marrow mesenchymal stem cells (BMSCs) as vectors. These exosomes are further modified with hyaluronic acid (HA) to form nanoplatforms (EXO/PB) that specifically target inflammation. HA binding enables EXO/PB to locate on M1 microglia, promoting ROS clearance and facilitating the transition from M1 phenotype to M2 phenotype. Our results show that EXO/PB not only targets M1 microglia, but also leverages the ROS clearance capabilities of Prussian blue nanozymes to influence this phenotypic transition. Finally, EXO/PB provides a new therapeutic strategy for the treatment of acute spinal cord injury.