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

作者：Mingyan Yang, Yawen Yu, Da‐Lei Li, Teng Liu, Zhixia Wang, Baifang Gong, Xinxin Bai, Yaping He, Hai‐Yue Liang, Huaying Fan · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70263 · 被引用次数：5 · 研究领域：Alzheimer's disease research and treatments、Nanoparticle-Based Drug Delivery、Advanced Nanomaterials in Catalysis

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....