Multiple sclerosis (MS) is a progressive chronic demyelinating and neurodegenerative disease. The symptoms could only be diminished through stimulated remyelination. Although administration of microRNA-219a-5P (miR-219) seems to recover the damages, it is hampered by the challenging delivery of genes to the central nervous system across the blood-brain barrier. To enhance the CNS delivery of miR-219, a novel non-viral targeted vector was appraised by conjugating chitosan (Ch) to tragacanthic acid (TA) and glutathione (Glu). The nanoparticles were characterized and injected into the cuprizone model of MS mice to investigate the in vivo features of the resulting polyplex. Transmission electron microscopy, luxol fast blue staining, and proteolipid protein 1 (Plp1) overexpression confirmed more compact myelin sheaths following the administration of the targeted miR-219 nanoparticles and positron emission tomography (PET) scan also demonstrated the reduced inflammation and higher cell regeneration in the brain. Fluorescence microscopy and in vivo imaging were employed to identify miR-219 accumulation patterns in mice. The polyplex led to miR-219 overexpression, crystallin alpha B upregulation, and apolipoprotein E downregulation. It was concluded that glutathione targeted Ch/TA nanoparticles could be exploited as a feasible non-viral vector for miR-219 specific targeting to the brain, miR-219 overexpression and inflammation abatement in MS.

多发性硬化症（MS）是一种进行性慢性脱髓鞘和神经退行性疾病。这些症状只能通过刺激髓鞘再生来减轻。尽管使用 microRNA-219a-5P (miR-219) 似乎可以恢复损伤，但它受到基因穿过血脑屏障传递到中枢神经系统的挑战性的阻碍。为了增强 miR-219 的 CNS 递送，通过将壳聚糖 (Ch) 与黄蓍胶 (TA) 和谷胱甘肽 (Glu) 缀合来评估新型非病毒靶向载体。对纳米颗粒进行表征，并将其注射到 MS 小鼠的铜宗模型中，以研究所得聚合复合物的体内特征。透射电子显微镜、luxol 坚蓝染色和蛋白脂质蛋白 1 (Plp1) 过表达证实，在施用靶向 miR-219 纳米粒子后，髓鞘更加致密，正电子发射断层扫描 (PET) 扫描也表明，炎症减轻，细胞再生加快。大脑。采用荧光显微镜和体内成像来鉴定小鼠中 miR-219 的积累模式。复合物导致 miR-219 过度表达、晶状体蛋白 α B 上调和载脂蛋白 E 下调。结论是，谷胱甘肽靶向 Ch/TA 纳米颗粒可用作可行的非病毒载体，用于 miR-219 特异性靶向大脑、miR-219 过表达和 MS 中的炎症减轻。