Academic Frontier
ACS Nano | Multifunctional Diselenide-Based Antioxidant Nanozymes Promote Spinal Cord Repair by Alleviating Oxidative Stress and Modulating Immunity
QQ Academic Group: 1092348845
Detailed
Spinal cord injury may trigger excessive reactive oxygen species (ROS) production and persistent inflammatory responses, both of which disrupt the neural repair process. Therefore, there is an urgent need for a therapeutic intervention that can both neutralize ROS and restore immune balance. This study reports a hyaluronic acid-based diselenide-crosslinked nanogel (Se–Se@HA), designed to integrate catalytic ROS scavenging and immunomodulatory capabilities to reconstruct the damaged microenvironment and promote repair. Se–Se@HA demonstrates remarkable structural stability and selectively responds to ROS, showing strong free radical scavenging ability. By inhibiting M1 polarization and enhancing the M2 phenotype, Se–Se@HA reduces levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, exhibiting potent anti-inflammatory effects. In vitro, Se–Se@HA protects neurons from oxidative stress-induced damage and promotes neurite outgrowth and axonal bridging. In vivo, this nanogel shows robust ROS scavenging and anti-inflammatory effects. Transcriptomic analysis reveals downregulation of NF-κB, TNF, and MAPK signaling pathways, alongside enrichment of genes related to synaptic transmission and regeneration. Functionally, Se–Se@HA significantly improves Basso Mouse Scale scores, gait indices, and gait regularity, enhances motor evoked potentials and electromyography signals, reduces muscle atrophy; it increases axonal continuity, restores serotonergic and synapse-related signaling at the injury site, and decreases scar formation. These findings suggest that Se–Se@HA is a multifunctional nanozyme platform capable of coordinating oxidative stress alleviation, immune homeostasis, and neural regeneration, offering a promising therapeutic strategy for spinal cord injury.
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