Glyconanoparticles allow pre-symptomatic in vivo imaging of brain disease.
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.
van Kasteren
Sander I
SI
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom.
Campbell
Sandra J
SJ
Serres
Sébastien
S
Anthony
Daniel C
DC
Sibson
Nicola R
NR
Davis
Benjamin G
BG
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001927:Brain Diseases / Q000175:diagnosis* / Q000473:pathology; D019040:E-Selectin / Q000032:analysis; D004730:Endothelium, Vascular / Q000473:pathology; D007249:Inflammation / Q000175:diagnosis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053758:Nanoparticles; D019007:P-Selectin / Q000032:analysis; D011134:Polysaccharides; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D019040:E-Selectin; D019007:P-Selectin; D011134:Polysaccharides