title: Brain microvessel endothelial cells responses to gold nanoparticles: In vitro pro-inflammatory mediators and permeability.
abstract: This report examined blood-brain barrier (BBB) related proinflammatory mediators and permeability changes in response to various sized gold nanoparticles (Au-NPs) (3, 5, 7, 10, 30 and 60 nm) in vitro using primary rat brain microvessel endothelial cells (rBMEC). The Au-NPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and laser Doppler velocimetry (LDV). The accumulation of Au-NPs was determined spectrophotometrically. The rBMEC cytotoxicity of Au-NPs was evaluated by cell proliferation assay (XTT) (concentration range 0.24-15.63 μg/cm², for 24 h). The time-dependent changes (0, 2, 4 and 8 h) of several proinflammatory mediators (IL-1β, IL-2, TNFα and PGE₂) were evaluated by ELISA. The smaller Au-NPs (3-7 nm) showed higher rBMEC accumulation compared to larger Au-NPs (10-60 nm), while only moderate decreased cell viability was observed with small Au-NPs (3 nm) at high concentrations (≥ 7.8 μg/cm²). Even though slight changes in cell viability were observed with small Au-NPs, the basal levels of the various proinflammatory mediators remained unchanged with all treatments except LPS (positive control). rBMEC morphology appeared unaffected 24 h after exposure to Au-NPs with only mild changes in fluorescein permeability indicating BBB integrity was unaltered. Together, these data suggest the responses of the cerebral microvasculature to Au-NPs have a significant relationship with the Au-NPs unique size-dependent physiochemical properties.
authors.affiliation: Neurochemistry Laboratory, Division of Neurotoxicology, National Center of Toxicological Research/FDA, Jefferson, Arkansas, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Trickler
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lantz
authors.forename: Richard C
authors.initials: RC
authors.lastname: Murdock
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Schrand
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Robinson
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Newport
authors.forename: John J
authors.initials: JJ
authors.lastname: Schlager
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Oldenburg
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: William
authors.initials: W
authors.lastname: Slikker
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology* / Q000187:drug effects*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D019793:Fluorescein; D006046:Gold / Q000493:pharmacokinetics / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008027:Light; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000166:cytology / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D012542:Scattering, Radiation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D006046:Gold; D015232:Dinoprostone; D019793:Fluorescein