Brain Targeting and Aβ Binding Bifunctional Nanoparticles Inhibit Amyloid Protein Aggregation in APP/PS1 Transgenic Mice
Brain Targeting and Aβ Binding Bifunctional Nanoparticles Inhibit Amyloid Protein Aggregation in APP/PS1 Transgenic Mice
复制标题
大脑靶向和 Aβ 结合双功能纳米颗粒抑制 APP/PS1 转基因小鼠中淀粉样蛋白聚集。
DOI：
10.1021/acschemneuro.1c00035
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发表时间：
2021-05-27
影响因子：
5
通讯作者：
Gao，Huiling
中科院分区：
文献类型：
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作者：
Zhang，Xiancheng;Zhang，Xiaoyu;Gao，Huiling
阿尔茨海默病（AD）是一种隐匿性和进行性神经退行性疾病，几乎没有改善疾病的治疗方法。多种多肽/蛋白质类药物具有神经保护作用，为AD的治疗带来了新的希望。然而，这些药物的应用受到限制，因为它们的低特异性和难以穿过血脑屏障。本文利用噬菌体展示技术，对Aβ寡聚体结合肽（KH）和脑靶向肽（IS）进行了鉴定。我们将这些肽结合起来，开发了一种双功能纳米颗粒（IS@NP/KH），用于将Aβ1-42寡聚体结合肽递送到大脑中。鼻内给予IS@NP/KH显著减轻了AD动物模型（APPswe/PS 1d 9双转基因小鼠）的认知和行为缺陷，并减少了脑中的Aβ沉积。我们的研究结果表明，鼻内IS@NP/KH给药可能是治疗AD的一种新的治疗策略。
Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disease with few disease-modifying treatments. A variety of peptide/protein drugs have neuroprotective effects, which brings new hope for the treatment of AD. However, the application of these drugs is limited because of their low specificity and difficulty in crossing the blood-brain barrier. Herein, using the phage display technology, we identified the Aβ oligomer binding peptide (KH) and the brain targeting peptide (IS). We combined these peptides to develop a bifunctional nanoparticle (IS@NP/KH) for the delivery of Aβ1-42 oligomer binding peptide into the brain. Intranasal administration of IS@NP/KH significantly attenuated the cognitive and behavioral deficits and reduced the Aβ deposition in the brain of an AD animal model (APPswe/PS 1d9 double-transgenic mice). Our results suggest that intranasal IS@NP/KH administration could be a novel therapeutic strategy for the treatment of AD.