Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with A beta Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer's Disease

doi:10.2147/IJN.S240953

	Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with A beta Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer's Disease
	Liu, Xiao-Ge 1,2; Zhang, Lun 1,2; Lu, Shuai 1; Liu, Dong-Qun 1,2; Zhang, Ling-Xiao 1,2; Yu, Xiao-Lin 1; Liu, Rui-Tian 1
刊名	INTERNATIONAL JOURNAL OF NANOMEDICINE
	2020
卷号	15 页码:4919-4932
关键词	magnetic resonance imaging diagnosis Alzheimer 's disease beta-amyloid oligomer class A scavenger receptor
ISSN号	1178-2013
DOI	10.2147/IJN.S240953
英文摘要	Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Diagnosing AD before symptoms arise will facilitate earlier intervention. The early diagnostic approaches are thus urgently needed. Methods: The multifunctional nanoparticles W20/XD4-SPIONs were constructed by the conjugation of oligomer-specific scFv antibody W20 and class A scavenger receptor (SR-A) activator XD4 onto superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs' stability and uniformity in size were measured by dynamic light scattering and transmission electron microscopy. The ability of W20/XD4-SPIONs for recognizing A beta oligomers (A beta Os) and promoting A beta Os phagocytosis was assessed by immunocytochemistry and flow cytometry analysis. The blood-brain barrier permeability of W20/XD4-SPIONs was determined by a co-culture transwell model. The in vivo probe distribution of W20/XD4-SPIONs in AD mouse brains was detected by magnetic resonance imaging (MRI). Results: W20/XD4-SPIONs, as an A beta Os-targeted molecular MRI contrast probe, readily reached pathological A beta Os regions in brains and distinguished AD transgenic mice from WT controls. W20/XD4-SPIONs retained the property of XD4 for SR-A activation and significantly promoted microglial phagocytosis of A beta Os. Moreover, W20/XD4-SPIONs exhibited the properties of good biocompatibility, high stability and low cytotoxicity. Conclusion: Compared with W20-SPIONs or XD4-SPIONs, W20/XD4-SPIONs show the highest efficiency for A beta Os-targeting and significantly enhance A beta Os uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to A beta Os in AD brains to provide an MRI signal, demonstrating that W20/XD4-SPIONs are promising diagnostic agents for early-stage AD. Due to the beneficial effect of W20 and XD4 on neuropathology, W20/XD4-SPIONs may also have therapeutic potential for AD.
资助项目	National Natural Science Foundation of China[81971610]
WOS关键词	MICROGLIA ; TAU ; HYPOTHESIS ; RECOGNIZE ; BIOMARKER ; CELLS ; FLUID
WOS研究方向	Science & Technology - Other Topics ; Pharmacology & Pharmacy
语种	英语
出版者	DOVE MEDICAL PRESS LTD
WOS记录号	WOS:000548715400002
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/41423]
专题	中国科学院过程工程研究所
通讯作者	Yu, Xiao-Lin; Liu, Rui-Tian
作者单位	1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Sch Chem & Chem Engn, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Liu, Xiao-Ge,Zhang, Lun,Lu, Shuai,et al. Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with A beta Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer's Disease[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2020,15:4919-4932.
APA	Liu, Xiao-Ge.,Zhang, Lun.,Lu, Shuai.,Liu, Dong-Qun.,Zhang, Ling-Xiao.,...&Liu, Rui-Tian.(2020).Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with A beta Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer's Disease.INTERNATIONAL JOURNAL OF NANOMEDICINE,15,4919-4932.
MLA	Liu, Xiao-Ge,et al."Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with A beta Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer's Disease".INTERNATIONAL JOURNAL OF NANOMEDICINE 15(2020):4919-4932.