A multifunctional and ROS response CO-gas delivery platform for spinal cord regeneration.

Area of Science:

• Neuroscience
• Biomedical Engineering
• Pharmacology

Background:

• Spinal cord injury (SCI) causes neuroinflammation and hypoxia, hindering functional recovery.
• Carbon monoxide (CO) has anti-inflammatory properties, but safe delivery remains a challenge.

Purpose of the Study:

• To develop and evaluate a targeted CO delivery system (COPH) for SCI treatment.
• To investigate COPH's efficacy in reducing neuroinflammation, hypoxia, and neuronal apoptosis.

Main Methods:

• COPH platform combines a CO donor (CORM-401), peptide dendrimer nanogels (PDNs), and a microglia-targeting ligand (HA).
• In vitro and in vivo studies assessed COPH's effects on inflammatory mediators, microglial polarization, hypoxia, oxidative stress, and neuronal apoptosis.
• Investigated COPH's mechanism involving NF-κB/p65 and Nrf2/HO-1 pathways.

Main Results:

• COPH selectively targets microglia, releasing CO and scavenging reactive oxygen species (ROS) in response to elevated ROS.
• COPH suppressed pro-inflammatory mediators (IL-1β, CD86) by inhibiting the NF-κB/p65 pathway and promoted M1-to-M2 microglial polarization.
• CO release alleviated local hypoxia and activated the Nrf2/HO-1 pathway, reducing oxidative stress and neuronal apoptosis.

Conclusions:

• COPH is an effective targeted CO delivery system for SCI.
• COPH attenuates inflammation, relieves hypoxia, and protects neurons, presenting a promising therapeutic strategy for neurotrauma.