巨噬細胞靶向的Mms6 mRNA脂質(zhì)納米顆粒促進小鼠創(chuàng)傷性脊髓損傷后的運動功能恢復(fù)

中文摘要：

創(chuàng)傷性脊髓損傷（SCI）會導(dǎo)致嚴重的中樞神經(jīng)系統(tǒng)損傷。損傷部位的M2型巨噬細胞對于SCI的恢復(fù)至關(guān)重要。我們之前的研究表明，轉(zhuǎn)染了來源于磁趨性細菌的Mms6基因的M2型巨噬細胞能夠抵抗鐵死亡，并促進SCI的恢復(fù)。為了克服M2型巨噬細胞移植的局限性，我們開發(fā)了針對巨噬細胞的脂質(zhì)納米顆粒（LNPs）封裝Mms6 mRNA（Mms6 mRNA-PS/LNPs）。評估了這些納米顆粒在SCI小鼠中的靶向效率及治療效果。靜脈注射Mms6 mRNA-PS/LNPs可將更多的Mms6 mRNA遞送至損傷部位的巨噬細胞，而相比Mms6 mRNA-LNP組，這導(dǎo)致運動功能恢復(fù)增強、損傷區(qū)域和瘢痕形成減少，并促進神經(jīng)元存活及神經(jīng)纖維修復(fù)。當(dāng)巨噬細胞被荷蘭Liposoma的氯膦酸鹽脂質(zhì)體清除時，這些效果消失。這些發(fā)現(xiàn)表明，針對巨噬細胞的Mms6 mRNA遞送是一種有前景的治療策略，有助于促進創(chuàng)傷性SCI患者的脊髓修復(fù)和運動功能恢復(fù)。

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.

論文信息：

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

期刊名稱：Science Advances

時間期卷：Vol 11, Issue 13(2025)

在線時間：2025年3月26日

DOI：10.1126/sciadv.ads2295

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體在小鼠創(chuàng)傷性脊髓損傷（SCI）模型種清除肝臟和脾臟巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances：巨噬細胞靶向的Mms6 mRNA脂質(zhì)納米顆粒促進小鼠創(chuàng)傷性脊髓損傷后的運動功能恢復(fù)

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細胞的材料和方法：

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.

巨噬細胞清除材料和方法文獻截圖：