Intranasal Administration of a Novel ApoE-Mimetic Peptide-Coated Gold Nanoparticles as Therapy for Ischemic Stroke

IF 4.8 1区 医学 Q1 NEUROSCIENCES
Ming-Yan Yang, Ya-Wen Yu, Da-Lei Li, Teng Liu, Zhi-Xia Wang, Bai-Fang Gong, Xin-Xin Bai, Ya-Ping He, Hai-Yue Liang, Hua-Ying Fan
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Abstract

Background

Discovering new drugs for ischemic stroke is an effective intervention that may address the significant unmet clinical need of stroke. There is increasing evidence indicating that apolipoprotein E (ApoE) can be a potential candidate for the treatment of ischemic stroke. A short ApoE peptide could maintain the anti-inflammation and neuroprotection of the intact protein. Herein, we synthetized a novel ApoE memetic peptide, referred to as CS15, and explored its efficacy and neuroprotection of its innovative formulation of gold nanoparticles (GNPs) in transient focal ischemia in rat.

Methods

We examined anti-inflammatory activities of CS15 using LPS-induced inflammatory response in BV2 cells and in mice. GNPs were prepared by citrate reduction method and surface modified with CS15 to generate CS15-coated GNPs (CS15-GNPs). The accumulation and distribution of CS15-GNPs in the brain were confirmed by detecting the gold amount and fluorescent intensity. The neuroprotection of CS15 and CS15-GNPs was evaluate using middle cerebral artery occlusion (MCAO) model.

Results

The results showed that CS15 exhibited more potent anti-inflammation than COG1410. GNPs are capable of transporting CS15 to the brain, expanding its duration of action. Intranasal administration of CS15-GNPs notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation in transient focal ischemia in rat, which had much higher efficiency than free CS15.

Conclusion

CS15-GNPs exhibited favorable neuroprotection and biosafety. This study develops an innovative ApoE-mimetic peptide-capped GNPs, which provides a potential strategy for the treatment of ischemic stroke.

Abstract Image

一种新型模拟apoe肽包被的金纳米颗粒鼻内治疗缺血性中风
背景发现治疗缺血性脑卒中的新药是一种有效的干预措施,可以解决脑卒中临床未满足的重大需求。越来越多的证据表明载脂蛋白E (ApoE)可能是缺血性卒中治疗的潜在候选药物。一个短的ApoE肽可以维持完整蛋白的抗炎和神经保护作用。在此,我们合成了一种新的ApoE模因肽CS15,并探讨了其创新配方金纳米颗粒(GNPs)对大鼠短暂局灶性缺血的疗效和神经保护作用。方法采用lps诱导的BV2细胞和小鼠炎症反应检测CS15的抗炎活性。采用柠檬酸还原法制备GNPs,并用CS15进行表面修饰,得到CS15包被的GNPs (CS15-GNPs)。通过检测金量和荧光强度,证实CS15-GNPs在脑内的积累和分布。采用大脑中动脉闭塞(MCAO)模型评价CS15和CS15- gnps的神经保护作用。结果CS15比COG1410具有更强的抗炎活性。GNPs能够将CS15运送到大脑,延长其作用时间。经鼻给药CS15- gnps可显著降低大鼠暂时性局灶性缺血的梗死面积和神经元损伤,改善神经功能,抑制脑炎症,其效果明显高于游离CS15。结论CS15-GNPs具有良好的神经保护作用和生物安全性。本研究开发了一种创新的apoe -模拟肽盖顶GNPs,为缺血性卒中的治疗提供了一种潜在的策略。
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来源期刊
CNS Neuroscience & Therapeutics
CNS Neuroscience & Therapeutics 医学-神经科学
CiteScore
7.30
自引率
12.70%
发文量
240
审稿时长
2 months
期刊介绍: CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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