Glyconanoparticles allow pre-symptomatic in vivo imaging of brain disease

Abstract

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.

Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system

“…The observed capacity of MAN to cross the BBB with reduced neurotoxicity is extremely promising for targeting diseases related to the CNS, such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. 7,49 In addition, the authors firmly believe that MAN represents a promising material vehicle to selectively destroy cancer cells, including brain tumors, mainly because those cells overexpress a number of receptors to albumin.…”

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

“…The aselective CA Gd-DTPA-BMA did not result in enhancement under the same conditions, showing that the blood-brain barrier was still intact. Van Kasteren et al have synthesized a series of dextran-coated iron oxide nanoparticles, decorated with oligosaccharides of increasing carbohydrate complexity [47]. It appeared that only the nanoparticles conjugated with sLe x itself, (GNP-sLe x ; FiguRe 9; 22) targeted activated brain endothelium.…”

Neurological disorders and therapeutics targeted to surmount the blood–brain barrier

“…Magnetic resonance imaging has shown increased accumulation of these targeted nanoparticles in an experimental autoimmune encephalomyelitis rat model. 162 A serious limitation of stroke therapy is systemic hemorrhage due to the nonspecificity of tissue plasminogen activator. Hence, nanodevices have been developed, consisting of tissue plasminogen activator-bound polystyrene latex nanoparticles modified with antifibrin antibody that is selective for clots, thus avoiding nonspecific activity.…”