title: Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.
abstract: The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.
authors: Biomedical Research Network, The Open University, Milton Keynes, United Kingdom.
authors: Radka
authors: R
authors: Gromnicova
authors: Heather A
authors: HA
authors: Davies
authors: Peddagangannagari
authors: P
authors: Sreekanthreddy
authors: Ignacio A
authors: IA
authors: Romero
authors: Torben
authors: T
authors: Lund
authors: Ivan M
authors: IM
authors: Roitt
authors: James B
authors: JB
authors: Phillips
authors: David K
authors: DK
authors: Male
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D004727:Endothelium / Q000378:metabolism; D005947:Glucose / Q000737:chemistry*; D006046:Gold / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D006046:Gold; D005947:Glucose