Imaging Early Endothelial Inflammation Following Stroke by Core Shell Silica Superparamagnetic Glyconanoparticles That Target Selectin

Abstract

Activation of the endothelium is a pivotal first step for leukocyte migration into the diseased brain. Consequently, imaging this activation process is highly desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that bind specifically to the endothelial transmembrane inflammatory proteins E and P selectin. Magnetic resonance imaging revealed that the targeted nanoparticles accumulated in the brain vasculature following acute administration into a clinically relevant animal model of stroke, though increases in selectin expression were observed in both brain hemispheres. Nonfunctionalized naked particles also appear to be a plausible agent to target the ischemic vasculature. The importance of these findings is discussed regarding the potential for translation into the clinic.

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

“…However, the contrast agent was not specific for P-selectin and did not give better results than control particles. Moreover, signals were reported equally increased throughout the brain (Farr et al, 2014).…”

“…68 Ga-Fucoidan) or by coupling contrast agents to ligands (e.g. fucoidan, antibodies, sialyl Lewis X ) (Jin et al, 2009;McAteer et al, 2012;Beziere et al, 2014;Farr et al, 2014;Li et al, 2014). In a stroke/neuroinflammation context, Pselectin has been targeted in molecular MRI studies, with disappointing results: P-selectin targeted USPIOs (ultrasmall particles of iron oxide) had a limited sensitivity and specificity in a mouse ischaemic stroke model (Jin et al, 2009) and a dual antibody-conjugated MPIOs, targeting both VCAM1 and P-selectin, did not show better images over single VCAM1 antibody-conjugated MPIOs in a model of acute inflammation in mice .…”

Recent advances in biosensing using magnetic glyconanoparticles

“…[36 ] reported the synthesis o f m agnetite glyconanoparticles functionalized with approximately 100 sialic acid copies per nanoparticle for the detection of β-amyloid aggregates by MRI. Similarly, amino-functionalized silica MNPs were modified with carboxylic groups and decorated with Lewis X (Le X ) and sialyl Le X (sLe X ) with use of the N-hydroxysuccinimide linker [37]. These glycoMNPs were used as a magnetic resonance contrast agent for imaging poststroke endothelial inflammation in mice.…”

“…This procedure allowed the synthesis of glycoMNPs bearing multiple (10 5 -10 7 ) copies of the tetrasaccharide sLe X , whose interaction with selectins plays a key role in the first stages of the inflammatory cascade. The resulting glyconanoparticles were successfully used for in vivo imaging of brain lesions (for a critical discussion regarding magnetic resonance applications of the glycoMNPs described in [37][38][39], see BImaging^).…”

Cellulose Nanocrystals as Advanced "Green" Materials for Biological and Biomedical Engineering

“…Glucose-coated gold nanoparticles with blood-brain barrier-permeable (BBB) neuropeptides have displayed interesting BBB permeability and bio-distribution, increasing the candidacy as a good positron emission tomography (PET) contrast agent for in vivo imaging of brain (Frigell et al, 2014). Silica-coated iron oxide core shell magnetic nanoparticle, functionalized with carbohydrate, have been used for in vivo imaging of brain, spleen, and liver through magnetic resonance imaging (MRI) (Farr et al, 2014). Multifunctional CNC conjugates, prepared using a quinolone fluorophore and carbohydrate ligands, have recently been studied for biorecognition of carbohydrate-binding proteins and bacterial imaging.…”