Date of Award

Fall 2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Committee Director

Christopher J. Osgood

Committee Member

Stephen Beebe

Committee Member

Lesley H. Greene

Abstract

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding ND biocompatibility. Macrophages are found in almost all tissues of the body and are key players in the vertebrate immune system, maintaining homeostasis and initiating immune response to a wide range of pathogens and foreign or host mediators. I hypothesized that ND can affect macrophages and interfere with their functions, and aimed to study interactions of ND with these cells to better understand the potential impact of ND on the immune system. My studies included monitoring both cultured and bone-marrow-derived macrophages in vitro after different exposure conditions and assessment of their effects on cellular processes using molecular laboratory techniques. Results showed that these particles do not significantly increase cell death or changes in cell morphology. These macrophages internalized ND via phagocytic and clathrin-dependent endocytosis in a time- and dose-dependent manner. The internalized ND localized to the cytoplasm without eliciting an inflammatory response in macrophages. Investigations on the macrophage functions showed that treatment of macrophages with ND did not affect their ability to respond to lipopolysaccharides. On the other hand, their endocytic activity was reduced significantly, irrespective of ND dose. Exposure of bone marrow cells to ND early during their differentiation did not affect their morphology or reduce the percent of cells expressing macrophage surface markers. Nonetheless, ND exposure reduced the number of surface markers expressed on each cell. My findings suggest that ND are not cytotoxic to macrophages at the tested concentrations, but they can interfere with macrophage functions and differentiation. Further studies are needed to explore the mechanisms by which ND suppress macrophages endocytic activity and expression of surface markers and the downstream impact of these suppressed immune functions. In addition, the effects of ND on other cells’ immune functions and expression of other immune mediators yet to be studied before concluding the immunotoxicity or compatibility of ND.

ISBN

9780355772616

Available for download on Friday, March 15, 2019

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