小胶质细胞
炎症
免疫系统
血脑屏障
神经保护
生物
跨细胞
药理学
细胞生物学
中枢神经系统
神经科学
免疫学
生物化学
细胞
内吞作用
作者
Peixin Liu,Tongyu Zhang,Yuxing Wu,Qinjun Chen,Chen Jiang,Chen Jiang
标识
DOI:10.1002/adma.202408729
摘要
Abstract The formidable protection of physiological barriers and unclear pathogenic mechanisms impede drug development for Alzheimer's disease (AD). As defenders of the central nervous system, immune‐metabolism function, and stemness of glial cells remain dormant during degeneration, representing a significant challenge for simultaneously targeting and modulating. Here, a modular nanoplatform is presented composed of peptide‐drug conjugates and an inflammation‐responsive core. The nanoplatform is transported through the blood‐brain barrier via transcytosis and disassembles in the oxidative stress microenvironment upon intravenous administration. The released drug‐conjugated modules can specifically target and deliver hydroxychloroquine (HCQ) and all‐trans retinoic acid (ATRA) to microglia and astrocytes, respectively. The immune function of chronic tolerant microglia is activated by metabolic modulation, and reactive astrocytes trans‐differentiate into functional neurons. In a transgenic mouse model, nanoplatform reduces levels of toxic proteins and inflammation while increasing neuronal density. This results in the amelioration of learning and memory decline. The modular nanoplatform provides design principles for multi‐cellular targeting and combination nano‐therapy for inflammation‐related diseases.
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