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.

中文翻译：

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新型纳米复合材料通过调节 NF-κB 介导的小胶质细胞极化改善脊髓损伤的功能恢复

促炎性小胶质细胞引起的继发性神经炎症加剧了脊髓损伤（SCI）患者的残疾，而低的给药效率降低了常规药物促进功能恢复的治疗效果。如今，采用纳米复合材料被认为是克服这一障碍的有前途的方法。在此，开发了中性粒细胞膜包被槲皮素的纳米颗粒（表示为 NQNP）来提高药物输送效率并重新极化小胶质细胞，从而抑制 SCI 中的继发性神经炎症。槲皮素负载纳米颗粒 (QNP) 具有将促炎性小胶质细胞重新编程为抗炎性小胶质细胞的能力，是 NQNP 的内核。中性粒细胞膜进一步涂覆在内核上，用于靶向药物输送和共中和炎症因子。体外和体内研究表明，NQNPs可以在活性氧（ROS）丰富的环境下可控释放槲皮素，通过核因子κ-B（NK-κB）途径将小胶质细胞极化重编程为M2表型，从而抑制过度的神经炎症，增加神经元的密度和功能状态，最终促进SCI的运动恢复，具有优异的生物相容性。我们相信当前的研究带来了一种新颖的策略，并为 SCI 的治疗提供了新的思路。