Macrophage Membrane-Coated MnO₂ Nanoparticles Provide Neuroprotection by Reducing Oxidative Stress after Spinal Cord Injury

Secondary injury following spinal cord injury (SCI) results in a large production of reactive oxygen species (ROS) (e.g., H 2 O 2 ) in the spinal cord microenvironment, which then leads to an excessive burst of inflammation and ultimately neuronal death. In this study, we prepared manganese dioxide (MnO 2 ) nanoparticles coated by macrophage membranes, named M@MnO 2, to cope with early ROS bursts in the SCI microenvironment. The biosafety and targeting ability of the MnO 2 nanoparticles were improved through the macrophage membranes. Successful preparation of M@MnO 2 was verified by transmission electron microscopy, Western blot, and dynamic light scattering. Small animal imaging showed that M@MnO 2 accumulated in large quantities at the site of SCI. In the early stages of SCI, M@MnO 2 effectively reduced the ROS content, as well as the hypoxia-inducible factor 1α (HIF-1α) content, malondialdehyde content, and superoxide anion content caused by ROS, further leading to a decrease in some of the proteins associated with inflammation at the site of SCI (CD11b, CD86, COX2, IL-1β, and iNOS), ultimately achieving neuroprotection and recovery of motor function.