title: The Endothelial Glycocalyx Controls Interactions of Quantum Dots with the Endothelium and Their Translocation across the Blood-Tissue Border.
abstract: 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.
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Bernd
authors.identifier: 0000-0002-2615-0803
authors.initials: B
authors.lastname: Uhl
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hirn
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Immler
authors.affiliation: Electron Microscopy Unit, Max Planck Institute for Molecular Biomedicine , 48149 Münster, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Mildner
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Möckl
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Sperandio
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bräuchle
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.|Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Reichel
authors.affiliation: Electron Microscopy Unit, Max Planck Institute for Molecular Biomedicine , 48149 Münster, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zeuschner
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 81377 Munich, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism*; D019276:Glycocalyx / Q000737:chemistry / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D045663:Quantum Dots / Q000737:chemistry / Q000378:metabolism*
keywords: blood−tissue border; endothelial glycocalyx; multiphoton in vivo microscopy; nanoparticles; nanoparticle−endothelium interactions; quantum dots; translocation