PDF(Pubmed)
Abstract：
In multiple sclerosis, lesions are formed in various areas of the CNS, which are characterized by reactive gliosis, immune cell infiltration, extracellular matrix changes and demyelination. CAQK peptide (peptide sequence: cysteine-alanine-glutamine-lysine) was previously introduced as a targeting peptide for the injured site of the brain. In the present study, we aimed to develop a multifunctional system using nanoparticles coated by CAQK peptide, to target the demyelinated lesions in animal model of multiple sclerosis. We investigated the binding of fluorescein amidite-labelled CAQK and fluorescein amidite-labelled CGGK (as control) on mouse brain sections. Then, the porous silicon nanoparticles were synthesized and coupled with fluorescein amidite-labelled CAQK. Five days after lysolecithin-induced demyelination, male mice were intravenously injected with methylprednisolone-loaded porous silicon nanoparticles conjugated to CAQK or the same amount of free methylprednisolone. Our results showed that fluorescein amidite-labelled CAQK recognizes demyelinated lesions in brain sections of animal brains injected with lysolecithin. In addition, intravenous application of methylprednisolone-loaded nanoparticle porous silicon conjugated to CAQK at a single dose of 0.24 mg reduced the levels of microglial activation and astrocyte reactivation in the lesions of mouse corpus callosum after 24 and 48 h. No significant effect was observed following the injection of the same dose of free methylprednisolone. CAQK seems a potential targeting peptide for delivering drugs or other biologically active chemicals/reagents to the CNS of patients with multiple sclerosis. Low-dose methylprednisolone in this targeted drug delivery system showed significant beneficial effect.
摘要：
在多发性硬化症中，病变形成在中枢神经系统的不同区域，以反应性神经胶质增生为特征，免疫细胞浸润，细胞外基质改变和脱髓鞘。先前引入CAQK肽(肽序列:半胱氨酸-丙氨酸-谷氨酰胺-赖氨酸)作为脑损伤部位的靶向肽。在本研究中,我们的目标是开发一种多功能系统，使用CAQK肽包被的纳米颗粒，以多发性硬化动物模型中的脱髓鞘性病变为目标。我们研究了氨基荧光素标记的CAQK和氨基荧光素标记的CGGK（作为对照）在小鼠脑切片上的结合。然后，合成了多孔硅纳米颗粒，并与荧光酰胺标记的CAQK偶联。溶血卵磷脂诱导脱髓鞘五天后，雄性小鼠静脉注射与CAQK偶联的负载甲基强的松龙的多孔硅纳米颗粒或等量的游离甲基强的松龙.我们的结果表明，荧光酰胺标记的CAQK可识别注射溶血卵磷脂的动物大脑中的脱髓鞘病变。此外,单剂量0.24mg的CAQK偶联的甲基强的松龙纳米颗粒在24和48h后，可降低小鼠call体病变中小胶质细胞活化和星形胶质细胞再活化的水平。注射相同剂量的游离甲基强的松龙后，未观察到显着效果。CAQK似乎是一种潜在的靶向肽，用于将药物或其他生物活性化学物质/试剂输送到多发性硬化症患者的CNS。低剂量甲基强的松龙在该靶向给药系统中显示出显著的有益效果。
