Precision Nanotherapy for Spinal Cord Injury: Modulating SLC16A3 With Methylprednisolone-Loaded Nanoparticles.

IF 3.8 2区 医学 Q1 CLINICAL NEUROLOGY Neurospine Pub Date : 2024-12-23 DOI:10.14245/ns.2448814.407
Jianwei Lv, Shibo Ma, Duo Shan
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Abstract

Objective: Spinal Cord Injury (SCI) leads to severe motor and sensory deficits, with limited treatment options. This study investigates how methylprednisolone-loaded nanoparticles (MP-NPs) modulate SCI repair by targeting Solute Carrier Family 16 Member 3 (SLC16A3) and reshaping the macrophage-inflammatory microenvironment.

Methods: Transcriptome data were analyzed to identify differentially expressed genes (DEGs) associated with SCI. Immune infiltration and WGCNA analyses identified genes linked to M2 macrophage polarization, pinpointing SLC16A3 as a key regulatory factor. MP-NPs were synthesized, characterized, and tested for their effects on macrophage polarization, neuronal protection, and SCI recovery in rats.

Results: We identified 612 DEGs related to inflammation and immune response in SCI. SLC16A3, upregulated in SCI, was downregulated by MP-NPs. In vitro, MP-NPs promoted M2 macrophage polarization, enhanced neuronal survival, and supported neural stem cell (NSC) differentiation. In vivo, MP-NPs significantly improved motor recovery, reduced inflammation, and facilitated neural repair in SCI rats.

Conclusion: MP-NPs downregulate SLC16A3 and modulate the macrophage-inflammatory environment, promoting neural repair and functional recovery in SCI, offering a promising therapeutic strategy.

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脊髓损伤的精准纳米疗法:用装载甲基强的松龙的纳米颗粒调节 SLC16A3。
目的:脊髓损伤(SCI)导致严重的运动和感觉缺陷,治疗选择有限。本研究探讨了甲基强龙负载纳米颗粒(MP-NPs)如何通过靶向溶质载体家族16成员3 (SLC16A3)和重塑巨噬-炎症微环境来调节SCI修复。方法:分析转录组数据,鉴定与SCI相关的差异表达基因(DEGs)。免疫浸润和WGCNA分析发现了与M2巨噬细胞极化相关的基因,确定SLC16A3是关键的调节因子。合成、表征MP-NPs,并测试其对大鼠巨噬细胞极化、神经元保护和脊髓损伤恢复的作用。结果:我们在脊髓损伤中鉴定出612个与炎症和免疫反应相关的基因。SLC16A3在SCI中上调,在MP-NPs中下调。在体外,MP-NPs促进M2巨噬细胞极化,增强神经元存活,支持神经干细胞(NSC)分化。在体内,MP-NPs显著改善脊髓损伤大鼠的运动恢复,减少炎症,促进神经修复。结论:MP-NPs下调SLC16A3并调节巨噬细胞炎症环境,促进脊髓损伤的神经修复和功能恢复,是一种很有前景的治疗策略。
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来源期刊
Neurospine
Neurospine Multiple-
CiteScore
5.80
自引率
18.80%
发文量
93
审稿时长
10 weeks
期刊最新文献
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