Inflammation-induced brain endothelial activation leads to uptake of electrostatically stabilized iron oxide nanoparticles via sulfated glycosaminoglycans

In mice with experimental autoimmune encephalomyelitis but not in healthy mice, very small superparamagnetic nanoparticles (VSOP) injected intravenously accumulated in endothelial cells in the brain in vivo (A). We demonstrate here that inflammatory mediators such as TNF-alpha led to alteration of endothelial glycocalyx, in particular of the sulfated glycosaminglycans (GAG) as illustrated in (B). VSOP interact with the modified sulfated GAGs in the brain vasculature and are uptaken by brain endothelial cells via clathrin-dependent endocytosis, also shown by transmission electron microscopy (B and C).651