Yang Ming-Yan, Yu Ya-Wen, Li Da-Lei, Liu Teng, Wang Zhi-Xia, Gong Bai-Fang, Bai Xin-Xin, He Ya-Ping, Liang Hai-Yue, Fan Hua-Ying
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.
Yantai Center for Food and Drug Control, Yantai, China.
CNS Neurosci Ther. 2025 Mar;31(3):e70263. doi: 10.1111/cns.70263.
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.
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.
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.
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.
发现用于缺血性中风的新药是一种有效的干预措施，可能满足中风尚未得到满足的重大临床需求。越来越多的证据表明，载脂蛋白E（ApoE）可能是治疗缺血性中风的潜在候选药物。一种短的ApoE肽可以维持完整蛋白质的抗炎和神经保护作用。在此，我们合成了一种新型的ApoE模拟肽，称为CS15，并探讨了其创新的金纳米颗粒（GNPs）制剂在大鼠短暂性局灶性缺血中的疗效和神经保护作用。
我们使用脂多糖诱导的BV2细胞和小鼠炎症反应来检测CS15的抗炎活性。通过柠檬酸盐还原法制备GNPs，并用CS15进行表面修饰以生成CS15包被的GNPs（CS15-GNPs）。通过检测金含量和荧光强度来确认CS15-GNPs在脑中的积累和分布。使用大脑中动脉闭塞（MCAO）模型评估CS15和CS15-GNPs的神经保护作用。
结果表明，CS15比COG1410表现出更强的抗炎作用。GNPs能够将CS15转运到大脑，延长其作用时间。经鼻给予CS15-GNPs可显著减小梗死面积和神经元损伤，改善神经功能，并抑制大鼠短暂性局灶性缺血中的脑部炎症，其效率比游离CS15高得多。
CS15-GNPs表现出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载脂蛋白E模拟肽封端的GNPs，为缺血性中风的治疗提供了一种潜在策略。
