Development of an anti-vascular cell adhesion protein-1 aptamer for molecular imaging and inflammation detection in transgenic mouse model of Alzheimer's disease

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DOIResolve DOI: http://doi.org/10.1166/jbn.2015.2154
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TypeArticle
Journal titleJournal of Biomedical Nanotechnology
ISSN1550-7033
Volume11
Issue12
Pages22642274; # of pages: 11
SubjectCell adhesion; Cells; Cytology; Diagnosis; Dissociation; Endothelial cells; Infrared devices; Mammals; Molecules; Neurodegenerative diseases; Pathology; Alzheimer's disease; Aptamers; Near-infrared fluorescence imaging; Therapeutic monitoring; Vascular cell adhesion; VCAM-1; Molecular imaging; amyloid beta protein; aptamer; cyanine dye 5 11R6; fluorescein; fluorescent dye; single stranded DNA; vascular cell adhesion molecule 1; animal experiment; animal model; animal tissue; cerebellum; DNA library; DNA sequence; electrophoretic mobility; fluorescence imaging; fluorescence microscopy; gel mobility shift assay; human; human cell; in vitro selection; in vivo study; mouse; nervous system inflammation; nonhuman; protein targeting; umbilical vein endothelial cell; disease model; fluorescence imaging; genetics; inflammation; metabolism; molecular imaging; nucleotide sequence; transgenic mouse; Aptamers, Nucleotide; Base Sequence; Disease Models, Animal; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Mice, Transgenic; Optical Imaging
AbstractCerebrovascular inflammation is often involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Non-invasive and sensitive molecular imaging of cerebrovascular inflammation biomarkers therefore represents a potential AD diagnostic and therapeutic monitoring method. Here, we describe the development of a novel aptamer-based near infrared fluorescence imaging probe targeting Vascular Cell Adhesion Molecule-1 (VCAM-1), an adhesion molecule overexpressed by the activated cerebrovasculature during inflammation. A SELEX-type screening of a random ssDNA library against human VCAM-1 identified a high-affinity ssDNA aptamer with a dissociation constant of 49 nM. We demonstrated that the Cy5.5-labeled aptamer binds to activated endothelial cells, with no affinity to nonactivated cells. A scrambled aptamer labeled with Cy5.5 did not image activated and non-activated endothelial cells, confirming the sequence specificity of the targeting. In vivo, the aptameric imaging agent targeting VCAM-1 successfully identified inflammation associated with amyloid-β plaques deposition in the vessels of the cerebellum of transgenic AD mice. It exhibited excellent retention by remaining bound to vessels 4 hours post-injection, indicating its effectiveness in in vivo imaging and its potential in early detection of cerebrovascular inflammation.
Publication date
PublisherAmerican Scientific Publishers
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics
Peer reviewedYes
NPARC number21277338
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Record identifierc5414c9b-5302-4caa-a514-b2759c8ba8a1
Record created2016-03-09
Record modified2016-05-09
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