Intraoperative application of an antioxidant nanoparticle-hydrogel targeting microglia regulates neuroinflammation in traumatic brain injury

  • J Nanobiotechnology. 2025 Sep 1;23(1):599. doi: 10.1186/s12951-025-03682-7.
Yuhan Han  #  1  2 ,  Jiacheng Gu  #  1  2 ,  Miaomiao Xu  #  3 ,  Yufei Ma  #  4 ,  Weiji Weng  #  1  2 ,  Qiyuan Feng  1  2 ,  Zhenghui He  1  2 ,  Wenlan Qi  1  2 ,  Qing Mao  1  2 ,  Jiyao Jiang  1  2 ,  Junfeng Feng  5  6
Affiliations
  • 1. Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Shanghai Institute of Head Trauma, Shanghai, China.
  • 3. Department of Nuclear Medicine, Shanghai Clinical Research and Trial Center, Shanghai, China.
  • 4. Department of Nuclear Medicine, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 6. Shanghai Institute of Head Trauma, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 40890874 DOI: 10.1186/s12951-025-03682-7
Abstract

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.

Keywords
Microglia; Nanoparticle-hydrogel; Neuroinflammation; ROS scavenging; Traumatic brain injury.
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