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Initial recruitment of leukocytes in inflammation associated with diseases such as multiple sclerosis (MS), ischemic stroke, and HIV-related dementia, takes place across intact, but activated brain endothelium. It is therefore undetectable to symptom-based diagnoses and cannot be observed by conventional imaging techniques, which rely on increased permeability of the blood-brain barrier (BBB) in later stages of disease. Specific visualization of the early-activated cerebral endothelium would provide a powerful tool for the presymptomatic diagnosis of brain disease and evaluation of new therapies. Here, we present the design, construction and in vivo application of carbohydrate-functionalized nanoparticles that allow direct detection of endothelial markers E-/P-selectin (CD62E/CD62P) in acute inflammation. These first examples of MRI-visible glyconanoparticles display multiple copies of the natural complex glycan ligand of selectins. Their resulting sensitivity and binding selectivity has allowed acute detection of disease in mammals with beneficial implications for treatment of an expanding patient population suffering from neurological disease.

Original publication

DOI

10.1073/pnas.0806787106

Type

Journal

Proc Natl Acad Sci U S A

Publication Date

06/01/2009

Volume

106

Pages

18 - 23

Keywords

Animals, Biomarkers, Brain, Brain Diseases, E-Selectin, Endothelium, Vascular, Inflammation, Magnetic Resonance Imaging, Male, Nanoparticles, P-Selectin, Polysaccharides, Rats, Rats, Wistar