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A Conditionally Releasable "Do not Eat Me" CD47 Signal Facilitates Microglia-Targeted Drug Delivery for the Treatment of Alzheimer's Disease
Zhang, Lun1,2; Liu, Xiao-ge1,2; Liu, Dong-qun1,2; Yu, Xiao-lin1; Zhang, Ling-xiao1,2; Zhu, Jie1; Lu, Shuai1; Liu, Rui-tian1
2020-04-29
Source PublicationADVANCED FUNCTIONAL MATERIALS
ISSN1616-301X
Pages10
Abstract

Efficient brain drug delivery has been a challenge in the treatment of Alzheimer's disease (AD) and other brain disorders as blood-brain barrier (BBB) impedes most drugs to reach brain. To overcome this obstacle, a novel poly(lactic-co-glycolic acid) (PLGA) nanoparticle conjugated with CD47 extracellular domain via reactive oxygen species (ROS)-responsive phenylborate ester bond exhibiting "do not eat me" signal and BBB penetrating peptide CRTIGPSVC (CRT) and microglia modulation agent Nec-1s encapsulated in it is developed. The experimental results show that the designed nanoparticle efficiently increases its half-life in blood circulation by preventing engulfment via phagocytes, and enhances its brain distribution by synergistic effect of CD47 and CRT. The high level of ROS in mouse brain releases CD47 from the nanoparticles and the resultant particles are effectively phagocytized by resident microglia. The engulfed Nec-1s modulates pathological microglia to a beneficial state, which reduces A beta burden, microgliosis and astrocytosis, decreases cytokine production and oxidative stress in the brains of AD mice, and finally attenuates cognition deficits and synapse loss. The results first demonstrate that the conditionally releasable "do not eat me" CD47 signal remarkably facilitates microglia-targeted drug delivery and warrants further study to develop therapeutic agent for AD treatment.

KeywordAlzheimer's Disease Brain Delivery Cd47 Microglia Ripk1
DOI10.1002/adfm.201910691
Language英语
WOS KeywordBlood-brain-barrier ; Peptides
Funding ProjectNational Natural Science Foundation of China[81971610] ; National Science and Technology Major Projects of New Drugs[2018ZX09733001-001-008]
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS SubjectChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
Funding OrganizationNational Natural Science Foundation of China ; National Science and Technology Major Projects of New Drugs
WOS IDWOS:000529145600001
PublisherWILEY-V C H VERLAG GMBH
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/40286
Collection中国科学院过程工程研究所
Corresponding AuthorLu, Shuai; Liu, Rui-tian
Affiliation1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Lun,Liu, Xiao-ge,Liu, Dong-qun,et al. A Conditionally Releasable "Do not Eat Me" CD47 Signal Facilitates Microglia-Targeted Drug Delivery for the Treatment of Alzheimer's Disease[J]. ADVANCED FUNCTIONAL MATERIALS,2020:10.
APA Zhang, Lun.,Liu, Xiao-ge.,Liu, Dong-qun.,Yu, Xiao-lin.,Zhang, Ling-xiao.,...&Liu, Rui-tian.(2020).A Conditionally Releasable "Do not Eat Me" CD47 Signal Facilitates Microglia-Targeted Drug Delivery for the Treatment of Alzheimer's Disease.ADVANCED FUNCTIONAL MATERIALS,10.
MLA Zhang, Lun,et al."A Conditionally Releasable "Do not Eat Me" CD47 Signal Facilitates Microglia-Targeted Drug Delivery for the Treatment of Alzheimer's Disease".ADVANCED FUNCTIONAL MATERIALS (2020):10.
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