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Title: Toxicology of nanoparticles after cellular uptake
Author: Cheng, Crystal
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Nanoscience is a multi-disciplinary field with the potential to both create new applications and understand existent systems, but its materials may be sources of toxicological concern. Understanding their toxic potential becomes essential to prevent any occupational, environmental, and consumer hazards. In this study, the toxicity of three different nanoparticles (NPs) was assessed: multi-walled carbon nanotubes (MWNTs), single-walled carbon nanotubes (SWNTs), and zinc oxide (ZnO) nanopowders. A combination of cell viability assays—NR, MTT, LDH, live dead—and microscopy—TEM, SEM, confocal—was used. No direct interactions occurred with any of the assays except the NR and ZnO nanopowders at > 50 µg/mL. The overall cytotoxic trend was ZnO > MWNT > SWNT. Both uncoated and PVA-coated ZnO nanopowders exhibited dose dependent toxicity with a sudden rate of increase between 12.5 and 25 µg/mL. Zn²+ cations appeared to be the major toxic source. Cytotoxic curves of ZnO nanopowders were similar to ZnCl2, a chemical known to dissociate into Zn²+ + Cl-, and a stereological analysis indicated specific mitochondrial damage, a condition associated with Zn²+ neurotoxicity. Zinc dissolution also increased with decreasing cell pH. Unpurified and purified MWNTs exhibited dose and time dependent toxicity with necrosis as the main mechanism of cell death. The residual iron Fe2O3 yielded no toxicity suggesting the nanotubes themselves as the toxic source. MWNTs entered cells both actively and passively and were found in the cytoplasm and nuclei. Only HiPco SWNTs caused significant cell death; none was observed for the unpurified and purified SWNTs. At the concentrations tested, this study found that both ZnO nanopowders and MWNTs caused acute toxicity while SWNTs were not acutely toxic. All three NPs should remain in the research and development stage until further studies can fully characterise their relationship with cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral