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巨噬细胞靶向的信使核糖核酸-脂质纳米颗粒促进小鼠创伤性脊髓损伤后的运动功能恢复。

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

作者信息

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

机构信息

Department of Orthopaedics of Sir Run Run Shaw Hospital and Department of Basic Medicine Sciences, Zhejiang University School of Medicine, Hangzhou 310016, PR China.

Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, PR China.

出版信息

Sci Adv. 2025 Mar 28;11(13):eads2295. doi: 10.1126/sciadv.ads2295. Epub 2025 Mar 26.

DOI:10.1126/sciadv.ads2295
PMID:40138430
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11939073/
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 gene can resist ferroptosis and enhance SCI recovery. To address the limitations of M2 macrophage transplantation, we developed lipid nanoparticles (LNPs) encapsulating mRNA targeting macrophages ( mRNA-PS/LNPs). The targeting efficiency and therapeutic effect of these LNPs in SCI mice were evaluated. Intravenous administration of mRNA-PS/LNPs delivered more mRNAs to lesion-site macrophages than those in the 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 mRNA is a promising therapeutic strategy for promoting spinal cord repair and motor function recovery in patients with traumatic SCI.

摘要

创伤性脊髓损伤(SCI)会导致严重的中枢神经系统损伤。损伤部位的M2巨噬细胞对SCI的恢复至关重要。我们之前的研究表明,转染了趋磁细菌衍生基因的M2巨噬细胞可以抵抗铁死亡并促进SCI恢复。为了解决M2巨噬细胞移植的局限性,我们开发了包裹靶向巨噬细胞的mRNA的脂质纳米颗粒(mRNA-PS/LNPs)。评估了这些LNPs在SCI小鼠中的靶向效率和治疗效果。静脉注射mRNA-PS/LNPs比mRNA-LNP组向损伤部位巨噬细胞递送了更多的mRNA,这导致运动功能恢复增强、损伤面积和瘢痕形成减少,并促进神经元存活和神经纤维修复。当巨噬细胞被清除时,这些作用消失。这些发现表明,巨噬细胞靶向递送mRNA是促进创伤性SCI患者脊髓修复和运动功能恢复的一种有前景的治疗策略。

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