Study on the Role of an Erythrocyte Membrane-Coated Nanotheranostic System in Targeted Immune Regulation of Alzheimer's Disease.
Study on the Role of an Erythrocyte Membrane-Coated Nanotheranostic System in Targeted Immune Regulation of Alzheimer's Disease.
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红细胞膜包被的纳米诊疗系统在阿尔茨海默病靶向免疫调节中的作用研究
DOI：
10.1002/advs.202301361
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发表时间：
2023-06
期刊：
影响因子：
15.1
通讯作者：
Nie, Xinmin
中科院分区：
文献类型：
--
作者：
Su, Yanrong;Huang, Yufen;Kou, Qinjie;Lu, Lu;Jiang, Haiye;Li, Xisheng;Gui, Rong;Huang, Rong;Huang, Xueyuan;Ma, Jinqi;Li, Jian;Nie, Xinmin
阿尔茨海默病(AD)是老年人最常见的神经退行性疾病之一。尽管阿尔茨海默病的病理生物学研究取得了重大进展，但仍没有有效的治疗方法。在这里，我们建立了一种红细胞膜伪装的纳米微球递送系统(TR-ZRA)，该系统由转铁蛋白受体适配子修饰，可以靶向穿过血脑屏障来改善AD免疫环境。在金属有机骨架的基础上，将CD22shRNA载体负载到tr-ZRA中，以沉默衰老小胶质细胞中异常高表达的CD22分子。更重要的是，TrZRA可增强小胶质细胞吞噬Aβ的能力，减轻补体激活，从而促进神经元活性，降低AD脑内炎症水平。此外，TR-ZRA还装载了Aβ适体，这使得在体外可以快速和低成本地监测Aβ斑块。经tr-ZRA治疗后，AD小鼠的学习和记忆能力得到增强。综上所述，本研究中的仿生递送纳米系统tr-ZRA为AD的治疗提供了一种有前途的策略和新的免疫靶点。设计了一种具有靶向适配子的红细胞膜包裹仿生纳米粒子(tr-ZRA)。该纳米颗粒可以靶向血脑屏障调节小胶质细胞中的基因，增强吞噬Aβ的能力，抑制补体激活水平，并在体外低成本、快速监测Aβ，为阿尔茨海默病的治疗提供了一种新的策略。
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the elderly population. Despite significant advances in studies of the pathobiology on AD, there is still no effective treatment. Here, an erythrocyte membrane‐camouflaged nanodrug delivery system (TR‐ZRA) modified with transferrin receptor aptamers that can be targeted across the blood–brain barrier to ameliorate AD immune environment is established. Based on metal‐organic framework (Zn‐CA), TR‐ZRA is loaded with CD22shRNA plasmid to silence the abnormally high expression molecule CD22 in aging microglia. Most importantly, TR‐ZRA can enhance the ability of microglia to phagocytose Aβ and alleviate complement activation, which can promote neuronal activity and decrease inflammation level in the AD brain. Moreover, TR‐ZRA is also loaded with Aβ aptamers, which allow rapid and low‐cost monitoring of Aβ plaques in vitro. After treatment with TR‐ZRA, learning, and memory abilities are enhanced in AD mice. In conclusion, the biomimetic delivery nanosystem TR‐ZRA in this study provides a promising strategy and novel immune targets for AD therapy. An erythrocyte membrane coated bionic nanoparticle (TR‐ZRA) with targeted aptamer is designed. The nanoparticle can be targeted into the blood–brain barrier to regulate genes in microglia, enhance the ability to phagocytose Aβ, inhibit the level of complement activation, and monitor Aβ in vitro low‐costly and rapidly, providing a new strategy for Alzheimer's disease treatment.
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