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

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-03-26 DOI:10.1126/sciadv.ads2295

Chunyan Fu, Xiaoqin Jin, Kangfan Ji, Ke Lan, Xingjia Mao, Zhaobo Huang, Jian Chen, Fengdong Zhao, Pengfei Li, Xuefei Hu, Liwen Sun, Ning Lu, Jinjie Zhong, Yingying Chen, Linlin Wang

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Abstract

Traumatic spinal cord injury (SCI) causes severe central nervous system damage. M2 macrophages within the lesion are crucial for SCI recovery. Our previous research revealed that M2 macrophages transfected with magnetotactic bacteria–derived Mms6 gene can resist ferroptosis and enhance SCI recovery. To address the limitations of M2 macrophage transplantation, we developed lipid nanoparticles (LNPs) encapsulating Mms6 mRNA targeting macrophages (Mms6 mRNA-PS/LNPs). The targeting efficiency and therapeutic effect of these LNPs in SCI mice were evaluated. 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, reducing lesion area and scar formation, and promoting neuronal survival and nerve fiber repair. These effects were nullified when macrophages were depleted. These 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.

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.