小胶质细胞
免疫系统
转铁蛋白受体
炎症
人口
适体
吞噬作用
血脑屏障
细胞生物学
免疫学
化学
神经科学
生物
癌症研究
受体
医学
中枢神经系统
分子生物学
生物化学
环境卫生
作者
Yanrong Su,Yu‐Fen Huang,Qinjie Kou,Lu Lu,Haiye Jiang,Xisheng Li,Rong Gui,Rong Huang,Xueyuan Huang,Jinqi Ma,Jian Li,Xinmin Nie
标识
DOI:10.1002/advs.202301361
摘要
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.
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