Han Yuhan, Gu Jiacheng, Xu Miaomiao, Ma Yufei, Weng Weiji, Feng Qiyuan, He Zhenghui, Qi Wenlan, Mao Qing, Jiang Jiyao, Feng Junfeng
Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Head Trauma, Shanghai, China.
J Nanobiotechnology. 2025 Sep 1;23(1):599. doi: 10.1186/s12951-025-03682-7.
Microglia play a critical role in neuroinflammation, a key secondary injury mechanism following traumatic brain injury (TBI). The colony-stimulating factor 1 receptor (CSF-1R) inhibitor PLX5622 has shown promise in suppressing neuroinflammation by depleting microglia, but it lacks specificity in targeting microglia at the injury site. To overcome this limitation, we developed PLX5622 nanoparticles functionalized with the CAQK peptide for lesion-specific targeting and combined them with a hydrogel (GelMA-PPS) that possesses potent reactive oxygen species (ROS) scavenging capabilities. This nanoparticle-hydrogel drug delivery system (GelMA-PPS/P) significantly enhanced the delivery efficiency and therapeutic efficacy of PLX5622 in TBI treatment. Localized administration of this system effectively depleted microglia at the injury site, suppressed neuroinflammation, and reduced the release of inflammatory cytokines. Its ROS scavenging ability was also validated in vitro and in vivo. Together, these effects synergistically improved neurological function recovery in TBI mouse models. This innovative strategy offers a comprehensive and targeted approach to managing neuroinflammation after TBI, providing a promising avenue for advancing TBI therapies.
小胶质细胞在神经炎症中起关键作用，神经炎症是创伤性脑损伤（TBI）后的一种关键继发性损伤机制。集落刺激因子1受体（CSF-1R）抑制剂PLX5622已显示出通过清除小胶质细胞来抑制神经炎症的潜力，但它在损伤部位靶向小胶质细胞方面缺乏特异性。为了克服这一局限性，我们开发了用CAQK肽功能化的PLX5622纳米颗粒用于损伤特异性靶向，并将它们与具有强大活性氧（ROS）清除能力的水凝胶（GelMA-PPS）相结合。这种纳米颗粒-水凝胶药物递送系统（GelMA-PPS/P）显著提高了PLX5622在TBI治疗中的递送效率和治疗效果。该系统的局部给药有效地清除了损伤部位的小胶质细胞，抑制了神经炎症，并减少了炎性细胞因子的释放。其ROS清除能力也在体外和体内得到了验证。这些作用共同协同改善了TBI小鼠模型的神经功能恢复。这种创新策略为管理TBI后的神经炎症提供了一种全面且有针对性的方法，为推进TBI治疗提供了一条有前景的途径。
