Publication Date

2013

Document Type

Dissertation

Committee Members

Nancy Bigley (Committee Member), David Goldstein (Committee Member), Saber Hussain (Committee Co-chair), Sharmila Mukhopadhyay (Committee Member), Courtney Sulentic (Committee Co-chair)

Degree Name

Doctor of Philosophy (PhD)

Abstract

Gold nanoparticles (Au-NPs) have demonstrated great potential in the development of a variety of tools with applications ranging from biomedical to military fields. Consequently, there is increasing concern regarding the toxic potential of these nanomaterials. Biodistribution studies demonstrate clearance of Au-NPs from peripheral circulation and bulk localization primarily in the liver and spleen post- intravenous administration. Deposition of Au-NPs in spleen suggests the potential for direct exposure of immune cells to these foreign materials under relatively static conditions. Although much less, due to the Blood Brain Barrier (BBB), Au-NPs appear to also deposit in the brain, suggesting that the resident cells of the brain may also be exposed to Au-NPs. Studies show the toxic potential of Au-NPs in a variety of cell types, however, the overall picture is still inconclusive due to the variation in cell-to-cell responses to these NPs. Additionally, NP aggregation and sedimentation in static in vitro conditions makes it very difficult to achieve uniformly dispersed treatment solutions. Furthermore, static conditions might be physiologically relevant to certain cell types, such as the immune cells in the spleen and lymph nodes; however the `BBB' experiences continuous flow of blood. Therefore, NP research calls for modification of traditional in vitro models to simulate the in vivo conditions. The main aim of this study was to determine the impact of Au-NPs on two model systems; 1) a B-lymphocyte cell line (CH12.LX) which pose as a direct target to NPs in vivo and 2) a co-culture of an astrocytic (C8-D30) and an endothelial cell line (bEnd.3), where endothelial cells shield the astrocytic cell line from direct exposure to NPs. Furthermore, static conditions might be physiologically relevant to certain cell types, such as the immune cells in the spleen and lymph nodes; however the `BBB' experiences continuous flow of blood. Our results demonstrate that treatment with Au-NPs lead to altered B-cell function, in terms of increased antibody expression, but no change in astrocytic and endothelial cell function was observed in terms of the inflammatory cytokine release. This might suggest that Au-NPs might exhibit differential response in different cell types which further emphasizes the need of careful evaluation of NPs before in vivo use. Furthermore, we observed decrease in agglomeration and deposition under flow conditions in comparison to static in vitro conditions suggesting improvement of traditional in vitro models to simulate the in vivo conditions.

Page Count

141

Department or Program

Biomedical Sciences

Year Degree Awarded

2013

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