Precision Nanotherapy for Spinal Cord Injury: Modulating SLC16A3 With Methylprednisolone-Loaded Nanoparticles.

OBJECTIVE

Spinal Cord Injury (SCI) leads to severe motor and sensory deficits, with limited treatment options. This study investigates how methylprednisolone-loaded nanoparticles (MP-NPs) modulate SCI repair by targeting Solute Carrier Family 16 Member 3 (SLC16A3) and reshaping the macrophage-inflammatory microenvironment.

METHODS

Transcriptome data were analyzed to identify differentially expressed genes (DEGs) associated with SCI. Immune infiltration and WGCNA analyses identified genes linked to M2 macrophage polarization, pinpointing SLC16A3 as a key regulatory factor. MP-NPs were synthesized, characterized, and tested for their effects on macrophage polarization, neuronal protection, and SCI recovery in rats.

RESULTS

We identified 612 DEGs related to inflammation and immune response in SCI. SLC16A3, upregulated in SCI, was downregulated by MP-NPs. In vitro, MP-NPs promoted M2 macrophage polarization, enhanced neuronal survival, and supported neural stem cell (NSC) differentiation. In vivo, MP-NPs significantly improved motor recovery, reduced inflammation, and facilitated neural repair in SCI rats.

CONCLUSION

MP-NPs downregulate SLC16A3 and modulate the macrophage-inflammatory environment, promoting neural repair and functional recovery in SCI, offering a promising therapeutic strategy.