Abstract |
Cerebrovascular 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 non-activated 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.
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Authors | Teresa Simao, Andy Ng, Dorothy Fatehi, Slavisa Corluka, Abedelnasser Abulrob, Mohammed Zourob |
Journal | Journal of biomedical nanotechnology
(J Biomed Nanotechnol)
Vol. 11
Issue 12
Pg. 2264-74
(Dec 2015)
ISSN: 1550-7033 [Print] United States |
PMID | 26510319
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aptamers, Nucleotide
- Vascular Cell Adhesion Molecule-1
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Topics |
- Alzheimer Disease
(complications, diagnosis)
- Animals
- Aptamers, Nucleotide
(genetics, metabolism)
- Base Sequence
- Disease Models, Animal
- Female
- Human Umbilical Vein Endothelial Cells
(metabolism)
- Humans
- Inflammation
(complications)
- Mice
- Mice, Transgenic
- Molecular Imaging
(methods)
- Optical Imaging
- Vascular Cell Adhesion Molecule-1
(metabolism)
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