Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease
Xiao-Ge Liu,1,2 Lun Zhang,1,2 Shuai Lu,1 Dong-Qun Liu,1,2 Ling-Xiao Zhang,1,2 Xiao-Lin Yu,1 Rui-Tian Liu1 1State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China; 2School of Chemistry and Ch...
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Dove Medical Press
2020
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oai:doaj.org-article:49836f48a7f140f5876909f0e95d06b12021-12-02T12:53:20ZMultifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease1178-2013https://doaj.org/article/49836f48a7f140f5876909f0e95d06b12020-07-01T00:00:00Zhttps://www.dovepress.com/multifunctional-superparamagnetic-iron-oxide-nanoparticles-conjugated--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiao-Ge Liu,1,2 Lun Zhang,1,2 Shuai Lu,1 Dong-Qun Liu,1,2 Ling-Xiao Zhang,1,2 Xiao-Lin Yu,1 Rui-Tian Liu1 1State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China; 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Science, Beijing 100049, People’s Republic of ChinaCorrespondence: Rui-Tian Liu; Xiao-Lin Yu Tel/ Fax +86 10 82545017; +86 10 82545075Tel/ Fax +86 10 82545025Email rtliu@ipe.ac.cn; yuxiaolin@ipe.ac.cnBackground: 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 Aβ oligomers (AβOs) and promoting AβOs 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 AβOs-targeted molecular MRI contrast probe, readily reached pathological AβOs 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 AβOs. 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 AβOs-targeting and significantly enhance AβOs uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to AβOs 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 .Keywords: magnetic resonance imaging, diagnosis, Alzheimer’s disease, β-amyloid, oligomer, class A scavenger receptorLiu XGZhang LLu SLiu DQZhang LXYu XLLiu RTDove Medical Pressarticlemagnetic resonance imagingdiagnosisalzheimer’s diseaseβ-amyloidoligomerclass a scavenger receptorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4919-4932 (2020) |
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DOAJ |
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EN |
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magnetic resonance imaging diagnosis alzheimer’s disease β-amyloid oligomer class a scavenger receptor Medicine (General) R5-920 |
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magnetic resonance imaging diagnosis alzheimer’s disease β-amyloid oligomer class a scavenger receptor Medicine (General) R5-920 Liu XG Zhang L Lu S Liu DQ Zhang LX Yu XL Liu RT Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease |
| description |
Xiao-Ge Liu,1,2 Lun Zhang,1,2 Shuai Lu,1 Dong-Qun Liu,1,2 Ling-Xiao Zhang,1,2 Xiao-Lin Yu,1 Rui-Tian Liu1 1State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China; 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Science, Beijing 100049, People’s Republic of ChinaCorrespondence: Rui-Tian Liu; Xiao-Lin Yu Tel/ Fax +86 10 82545017; +86 10 82545075Tel/ Fax +86 10 82545025Email rtliu@ipe.ac.cn; yuxiaolin@ipe.ac.cnBackground: 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 Aβ oligomers (AβOs) and promoting AβOs 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 AβOs-targeted molecular MRI contrast probe, readily reached pathological AβOs 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 AβOs. 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 AβOs-targeting and significantly enhance AβOs uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to AβOs 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 .Keywords: magnetic resonance imaging, diagnosis, Alzheimer’s disease, β-amyloid, oligomer, class A scavenger receptor |
| format |
article |
| author |
Liu XG Zhang L Lu S Liu DQ Zhang LX Yu XL Liu RT |
| author_facet |
Liu XG Zhang L Lu S Liu DQ Zhang LX Yu XL Liu RT |
| author_sort |
Liu XG |
| title |
Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease |
| title_short |
Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease |
| title_full |
Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease |
| title_fullStr |
Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease |
| title_full_unstemmed |
Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease |
| title_sort |
multifunctional superparamagnetic iron oxide nanoparticles conjugated with aβ oligomer-specific scfv antibody and class a scavenger receptor activator show early diagnostic potentials for alzheimer’s disease |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/49836f48a7f140f5876909f0e95d06b1 |
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1718393560405901312 |