Advances
in the engineering of nanoparticles (NPs), which represent
particles of less than 100 nm in one external dimension, led to an
increasing utilization of nanomaterials for biomedical purposes. A
prerequisite for their use in diagnostic and therapeutic applications,
however, is the targeted delivery to the site of injury. Interactions
between blood-borne NPs and the vascular endothelium represent a critical
step for nanoparticle delivery into diseased tissue. Here, we show
that the endothelial glycocalyx, which constitutes a glycoprotein–polysaccharide
meshwork coating the luminal surface of vessels, effectively controls
interactions of carboxyl-functionalized quantum dots with the microvascular
endothelium. Glycosaminoglycans of the endothelial glycocalyx were
found to physically cover endothelial adhesion and signaling molecules,
thereby preventing endothelial attachment, uptake, and translocation
of these nanoparticles through different layers of the vessel wall.
Conversely, degradation of the endothelial glycocalyx promoted interactions
of these nanoparticles with microvascular endothelial cells under
the pathologic condition of ischemia–reperfusion, thus identifying
the injured endothelial glycocalyx as an essential element of the
blood–tissue border facilitating the targeted delivery of nanomaterials
to diseased tissue