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-Ge1,2; Zhang, Lun1,2; Lu, Shuai1; Liu, Dong-Qun1,2; Zhang, Ling-Xiao1,2; Yu, Xiao-Lin1; Liu, Rui-Tian1 | |
刊名 | INTERNATIONAL JOURNAL OF NANOMEDICINE
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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. |
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