Macrophage-targeted Mms6 mRNA-lipid nanoparticles promote locomotor functional recovery after traumatic spinal cord injury in mice

Science Advances, 2025 · DOI: 10.1126/sciadv.ads2295 · Published: March 26, 2025

Simple Explanation

Traumatic spinal cord injury (SCI) causes severe central nervous system damage, and M2 macrophages are crucial for SCI recovery. The study developed lipid nanoparticles (LNPs) encapsulating Mms6 mRNA targeting macrophages (Mms6 mRNA-PS/LNPs) to enhance motor function recovery after SCI. Intravenous administration of Mms6 mRNA-PS/LNPs delivered more Mms6 mRNAs to lesion-site macrophages, enhancing motor function recovery and reducing lesion area and scar formation.

Study Duration

28 days

Participants

Female C57BL/6 mice (8 to 12 weeks, 20 to 25 g)

Evidence Level

Level I: Experimental study in mice

Key Findings

1
Mms6 mRNA-LNPs improved anti-ferroptosis capabilities of macrophages via managing the balance of cellular iron metabolism in a hypoxic condition, which is common in SCI.
2
Intravenous injection of Mms6 mRNA-LNPs promoted locomotor function recovery and morphological repair of the injured spinal cord in a dose-dependent manner.
3
Macrophage-targeted Mms6 mRNA-PS/LNPs could strengthen the effect of the Mms6 mRNA-loaded LNP delivery system on improvement in functional recovery and morphology repair in SCI mice.

Research Summary

This study engineered Mms6 mRNA-loaded LNPs for targeted delivery to macrophages and investigated whether these LNPs could promote locomotor functional recovery following SCI. Intravenous administration of Mms6 mRNA-PS/LNPs delivered more Mms6 mRNAs to lesion-site macrophages than those in the Mms6 mRNA-LNP group, which resulted in enhancing motor function recovery. The findings suggest that macrophage-targeted delivery of Mms6 mRNA is a promising therapeutic strategy for promoting spinal cord repair and motor function recovery in patients with traumatic SCI.

Practical Implications

Therapeutic Strategy

Macrophage-targeted Mms6 mRNA delivery could be a promising therapeutic strategy for promoting spinal cord repair and motor function recovery.

Delivery Method

PS-modified LNPs enable direct delivery of mRNA to endogenous cells, potentially eliminating the need for traditional cell transplantation and enhancing inherent repair mechanisms.

Clinical Translation

PS-modified LNP delivery systems might help translate biomedical achievements into clinical practice for central nervous system diseases.

Study Limitations

1
Many LNPs were still taken up in the spleen.
2
Need to search for more specific membrane molecules for macrophages.
3
Further optimizing the size, charge, and other characteristics of LNPs is needed.

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