Novel nanocomposites improve functional recovery of spinal cord injury by regulating NF-κB mediated microglia polarization

Secondary neuroinflammation caused by proinflammatory microglia exacerbates the disability of patients with spinal cord injury (SCI), while low drug delivery efficiency reduces the therapeutic effect of conventional drugs on promoting functional recovery. Nowadays, resorting to nanocomposites has been regarded as a promising approach to overcome such an obstacle. Herein, neutrophil membrane-coated quercetin-loaded nanoparticles (denoted NQNPs) were developed to improve drug delivery efficiency and repolarize microglia thereby inhibiting secondary neuroinflammation in SCI. Quercetin-loaded nanoparticles (QNPs), which have the capacity to reprogram proinflammatory microglia toward anti-inflammatory microglia, act as the inner core of NQNPs. The neutrophil membrane was further coated onto the inner core for targeted drug delivery and co-neutralizing inflammatory factors. In vitro and in vivo studies demonstrated that NQNPs could controllably release quercetin under the reactive oxygen species (ROS) abundant environment, reprogram microglia polarization toward M2 phenotype via nuclear factor kappa-B (NK-κB) pathway, thereby inhibiting excessive neuroinflammation, increasing the density and functional status of neurons, and finally promoting motor recovery of SCI with outstanding biocompatibility. We believe that the current research brings a novel strategy and sheds new light on the treatment of SCI.