Spatiotemporal Targeted Delivery of Biomimetic Bacterial Outer Membrane Nanoparticles for Enhanced Spinal Cord Injury Repair

Abstract Spinal cord injury (SCI) is a complex and dynamic pathological condition characterized by disrupted lipid metabolism and neuroinflammatory responses, posing significant therapeutic challenges. To address these, biomimetic bacterial outer membrane nanoparticles (BM‐NPs) are designed by integrating the precise targeting capability of detoxified outer membrane vesicles (dOMVs) with the efficient drug‐loading properties of liposomes. BM‐NPs exhibit superior targeting efficiency toward peripheral neutrophils and macrophages, enabling spatiotemporal drug delivery via immune cells. An innovative “Tortoise and Hare” dynamic adaptive delivery strategy is introduced, where neutrophils facilitate rapid drug transport during the acute phase of SCI, while macrophages ensure sustained delivery during the subacute phase. This strategy aligns with the dynamic pathological progression of SCI, offering precision targeting tailored to different stages of injury. BM‐NPs demonstrate multifaceted therapeutic effects, including the suppression of foam cell formation through coordinated enhancement of lipid droplet autophagy and cholesterol efflux. Furthermore, they modulate the inflammatory microenvironment, preserve myelin integrity, and significantly promote neural functional recovery post‐SCI. By overcoming the limitations of conventional delivery systems in targeting and timeliness, BM‐NPs offer an innovative, highly efficient, and clinically translatable platform for SCI treatment and other acute inflammatory disorders of the central nervous system.