title: Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues.
abstract: The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia. Kidney endothelium (ciGENC) showed higher uptake of these nanoparticles than brain endothelium (hCMEC/D3), reflecting their biodistribution in vivo. Nanoparticle uptake and subcellular localisation was quantified by transmission electron microscopy. The rate of internalisation was approximately 4x higher in kidney endothelium than brain endothelium. Vesicular endocytosis was approximately 4x greater than cytosolic uptake in both cell types, and endocytosis was blocked by metabolic inhibition, whereas cytosolic uptake was energy-independent. The cellular basis for the different rates of internalisation was investigated. Morphologically, both endothelia had similar profiles of vesicles and cell volumes. However, the rate of endocytosis was higher in kidney endothelium. Moreover, the glycocalyces of the endothelia differed, as determined by lectin-binding, and partial removal of the glycocalyx reduced nanoparticle uptake by kidney endothelium, but not brain endothelium. This study identifies tissue-specific properties of vascular endothelium that affects their interaction with nanoparticles and rate of transport.
authors: Department of Life, Health and Chemical Sciences, The Open University, Milton Keynes, United Kingdom.
authors: Radka
authors: R
authors: Gromnicova
authors: Department of Physiology, Koc University School of Medicine, Istanbul, Turkey.
authors: Mehmet
authors: M
authors: Kaya
authors: Department of Life, Health and Chemical Sciences, The Open University, Milton Keynes, United Kingdom.
authors: Ignacio A
authors: IA
authors: Romero
authors: Midatech Pharma plc, Abingdon, United Kingdom.
authors: Phil
authors: P
authors: Williams
authors: School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors: Simon
authors: S
authors: Satchell
authors: Department of Neurology, University of Sheffield, Sheffield, United Kingdom.
authors: Basil
authors: B
authors: Sharrack
authors: Department of Life, Health and Chemical Sciences, The Open University, Milton Keynes, United Kingdom.
authors: David
authors: D
authors: Male
mesh_terms: D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D011134:Polysaccharides; D011092:Polyethylene Glycols; D006046:Gold