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巨噬细胞靶向的Mms6 mRNA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

更新时间:2026-03-27   点击次数:13次

中文摘要:

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型巨噬细胞对于SCI的恢复至关重要。我们之前的研究表明,转染了来源于磁趋性细菌的Mms6基因的M2型巨噬细胞能够抵抗铁死亡,并促进SCI的恢复。为了克服M2型巨噬细胞移植的局限性,我们开发了针对巨噬细胞的脂质纳米颗粒(LNPs)封装Mms6 mRNA(Mms6 mRNA-PS/LNPs)。评估了这些纳米颗粒在SCI小鼠中的靶向效率及治疗效果。静脉注射Mms6 mRNA-PS/LNPs可将更多的Mms6 mRNA递送至损伤部位的巨噬细胞,而相比Mms6 mRNA-LNP组,这导致运动功能恢复增强、损伤区域和瘢痕形成减少,并促进神经元存活及神经纤维修复。当巨噬细胞被荷兰Liposoma的氯膦酸盐脂质体清除时,这些效果消失。这些发现表明,针对巨噬细胞的Mms6 mRNA递送是一种有前景的治疗策略,有助于促进创伤性SCI患者的脊髓修复和运动功能恢复。


英文摘要:

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.

论文信息:

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

期刊名称:Science Advances

时间期卷:Vol 11, Issue 13(2025)

在线时间:2025年3月26日

DOI:10.1126/sciadv.ads2295

产品信息:

货号:CP-005-005

规格:5ml+5ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes&Control Liposomes

办事处:靶点科技


Clodronate Liposomes氯膦酸盐脂质体在小鼠创伤性脊髓损伤(SCI)模型种清除肝脏和脾脏巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances:巨噬细胞靶向的Mms6 mRNA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

巨噬细胞靶向的Mms6 mRNA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


Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:

Macrophage depletion and evaluation of depletion efficiency

Macrophages were depleted by injection of clodronate-contained liposomes (Clodrosome) into mice (Liposoma B.V., Amsterdam, The Netherlands) according to a previously published protocol (40). C57BL/6J mice were intravenously injected with 0.2 ml of Clodrosome (5 mg/ml). Mice treated with PBS-containing liposomes without clodronate were used as controls. Flow cytometry and immunohistochemistry were used to assess the efficiency of macrophage depletion in the liver and spleen of mice at 0, 24, 48, and 72 hours after Clodrosome treatment using a mouse anti-F4/80 antibody (ab111101, Abcam; 1:100). Then, the optimal timing of maximum depletion was chosen for further study.


巨噬细胞清除材料和方法文献截图:

巨噬细胞靶向的Mms6 mRNA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


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