Nanoparticle delivery of CD68 siRNA inhibits neuroimmune responses by inhibiting activation of M1 macrophages.

CD68 is a vital costimulatory molecule expressed on macrophages/microglia (M/Ms) and plays a critical role in their activation. By targeting this molecule, therapeutic interventions can potentially prevent the homing of M/Ms. to the lesion site. In this study, we developed a biomimetic nanoparticle-based system (siCD68/NPs) to deliver CD68 small interfering RNA (siCD68) more efficiently into M/Ms.Administration of siCD68/NPs was found to not only polarize M1 macrophages toward M2 phenotype, but also reduce the reactive oxygen species (ROS) levels in lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) induced macrophages/microglia (M/Ms). Moreover, treatment with siCD68/NPs significantly extended the survival time in a mouse spinal cord injury (SCI) model.In summary, siCD68/NPs were found to activate an anti-neuroinflammatory immune response and reprogram the polarization of M/Ms., leading to a significant improvement in the recovery of spinal cord injury. This study contributes to the field of biomimetic nanoparticle-based therapies and offers novel insights into potential treatments for neuroinflammation-induced SCI.