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.

Keywords::

• Blood-brain-barrier
• neuroinflammation
• gold nanoparticles
• brain microvessel endothelial cells
• neurotoxicity

Acknowledgements

This research was supported in part by an appointment to the Postgraduate Research Participation Program with the U. S. Air Force Research Laboratory at the National Center for Toxicological Research/FDA (Jefferson, AR) administered by the Oak Ridge Institute of Science and Education (Oak Ridge, TN) through an interagency agreement between U.S. Department of Energy, U. S. Air Force Research Laboratory/RHPB and the U. S. Food and Drug Administration/NCTR.

Declaration of interest: The authors report no conflict of interest. The authors are responsible for the content and writing of the manuscript and does not necessarily reflect the position of the Government or FDA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.