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THE SIZE AND SURFACE COATING OF NANOSILVER DIFFERENTIALLY AFFECTS BIOLOGICAL ACTIVITY IN BLOOD BRAIN BARRIER (RBEC4) CELLS.
Mosher, S., S. SIMMONS, W. Ward, A. Fisher, B. Vallant, B. Chorley, AND B. VERONESI. THE SIZE AND SURFACE COATING OF NANOSILVER DIFFERENTIALLY AFFECTS BIOLOGICAL ACTIVITY IN BLOOD BRAIN BARRIER (RBEC4) CELLS. Presented at Society of Toxicology (SOT) Annual Meeeting, San Francisco, CA, March 11 - 15, 2012.
This research examines the relationships between the biological activity (i.e. translocation) of nanosilver (a high volume engineered nanomaterial) and its physical poroperties. Such information helps in the design of safer and more efficacious nanomaterials and more importantly are needed for effective risk assessment.
Linking the physical properties of nanoparticles with differences in their biological activity is critical for understanding their potential toxicity and mode of action. The influence of aggregate size, surface coating, and surface charge on nanosilver's (nanoAg) movement through confluent rat brain endothelial cells (RBEC4) was examined. Commercially available nanoAg of different sizes (10 nm, 75 nm) and surface coatings (PVP, citrate) were exposed (3.0-6.0 ppm) to monolayers of RBEC4 grown on coverslips or in transwell chambers. Microscopy (confocal, TEM) indicated that nanoAg particles translocate through barrier cells at different rates (30 min -3 hr) without disrupting their tight junctions. Changes in transcellular electrical resistance (TERS) indicated that surface coating (PVP>citrate) and small aggregate size (10 nm>75 nm) facilitated this movement (15-30 min). Reporter genes (AP-l, ARE), transfected into RBEC4 cells were significantly stimulated by 10 nm PVP "capped" nanoAg (1 ppm, 18 hr), relative to the other nanoAg materials. The genomic response of the cells to each nanoAg was also examined using Illumina Expression BeadChips. PCA analysis indicated that the number and types of transcripts activated by 10nm PVP were significantly distinct from the other experimental treatments. Bioinformatic analysis (KEGG analysis, IPA) indicated that pathways activated by the PVP 10 nm nanoAg were associated with endocytosis, bio-energetics and oxidative stress-mediated neurodegenerative (SLCA21) diseases. Future experiments will examine the relationship of nanoAg's physical properties and genomic events in brain cells (e.g., microglia, neurons) that are potential targets. (This abstract has been reviewed by NHEERL and does not necessarily reflect EPA policy)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH