Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform

Spinal cord injury (SCI) often leads to motor and sensory deficits. Excessive reactive oxygen species (ROS) severely damage neurons in the early and middle stages of SCI. Most antioxidants can't consistently eliminate ROS at non-toxic doses, compromising treatment. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but toxicity limits their use. This research proposes a synergistic therapeutic strategy using SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to boost ROS scavenging. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to enhance antioxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, regulating inflammatory factor expression and macrophage polarization into M2 phenotype. Additionally, they promoted neuronal maturation and axon growth by activating WNT4-dependent pathways, while preventing glial scar formation. This study demonstrates FSZ NPs' versatile bioactive functions for SCI treatment.

• 1
  SeNPs@ZIF-8 nanoparticles, particularly medium-sized ones (SSe@ZIF-8), exhibit enhanced ROS scavenging ability compared to SeNPs alone, reducing cytotoxicity.
• 2
  FSZ NPs (Fer-1@SSe@ZIF-8) prevent apoptosis and maintain mitochondrial homeostasis in nerve cells exposed to oxidative stress, protecting them from cell death induced by ROS.
• 3
  FSZ NPs promote neurite outgrowth and neuronal maturation by activating the WNT4/β-catenin pathway, leading to increased expression of neuronal markers and inhibition of glial cell formation.