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., H2O2) 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 (MnO2) nanoparticles coated by macrophage membranes, named M@MnO2, to cope with early ROS bursts in the SCI microenvironment. The biosafety and targeting ability of the MnO2 nanoparticles were improved through the macrophage membranes. Successful preparation of M@MnO2 was verified by transmission electron microscopy, Western blot, and dynamic light scattering. Small animal imaging showed that M@MnO2 accumulated in large quantities at the site of SCI. In the early stages of SCI, M@MnO2 effectively reduced the ROS content, as well as the hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-1 beta, and iNOS), ultimately achieving neuroprotection and recovery of motor function.