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Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer’s disease treatment by anti-neuroinflammation and neuroprotection
He, Xueqin1; Wang, Xiaorong1; Yang, Lianyi1; Yang, Zhihang1; Yu, Wenqi1; Wang, Yazhen1; Liu, Rui1; Chen, Meiwan2; Gao, Huile1
2022-04
Source PublicationGoogle scholar
ISSN2211-3835
Volume12Issue:4Pages:1987-1999
Abstract

The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu&FK@RNPs), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain. Meanwhile, these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS. As a result, the cognition of AD mice was significantly improved and the quantity of Aβ plaques was decreased. Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons. Besides, the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1β in the brain. Overall, Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion. Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.

KeywordReceptor For Advanced Glycation End Products Ros-responsive Blood‒brain Barrier Transcytosis Alzheimer's Disease Drug Combination Anti-neuroinflammation Neuroprotection Nano Drug Delivery System
DOIhttps://doi.org/10.1016/j.apsb.2022.02.001
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorGao, Huile
Affiliation1.Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharm
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
Recommended Citation
GB/T 7714
He, Xueqin,Wang, Xiaorong,Yang, Lianyi,et al. Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer’s disease treatment by anti-neuroinflammation and neuroprotection[J]. Google scholar,2022,12(4):1987-1999.
APA He, Xueqin,Wang, Xiaorong,Yang, Lianyi,Yang, Zhihang,Yu, Wenqi,Wang, Yazhen,Liu, Rui,Chen, Meiwan,&Gao, Huile.(2022).Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer’s disease treatment by anti-neuroinflammation and neuroprotection.Google scholar,12(4),1987-1999.
MLA He, Xueqin,et al."Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer’s disease treatment by anti-neuroinflammation and neuroprotection".Google scholar 12.4(2022):1987-1999.
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