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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
2022-04-01
Source PublicationActa Pharmaceutica Sinica B
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.

KeywordAlzheimer's Disease Anti-neuroinflammation Blood‒brain Barrier Transcytosis Drug Combination Nano Drug Delivery System Neuroprotection Receptor For Advanced Glycation End Products Ros-responsive
DOI10.1016/j.apsb.2022.02.001
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000808331500006
Scopus ID2-s2.0-85125481807
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
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, Sichuan University, Chengd
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]. Acta Pharmaceutica Sinica B,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.Acta Pharmaceutica Sinica B,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".Acta Pharmaceutica Sinica B 12.4(2022):1987-1999.
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