Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aß Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer's Disease.
Int J Nanomedicine
; 15: 4919-4932, 2020.
Article
em En
| MEDLINE
| ID: mdl-32764925
ABSTRACT
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 Aß oligomers (AßOs) and promoting AßOs 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 AßOs-targeted molecular MRI contrast probe, readily reached pathological AßOs 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 AßOs. 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 AßOs-targeting and significantly enhance AßOs uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to AßOs 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 .Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Imunoconjugados
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Receptores Depuradores
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Anticorpos de Cadeia Única
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Nanopartículas de Magnetita
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Doença de Alzheimer
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article