Nanomaterial toxicity is a major concern and could potentially hamper the progress of biomedical nanotechnology development. Dispelling these concerns requires that the consequences of nanomaterial exposure are evaluated, and the findings will determine whether developmental hurdles can be overcome.
This thesis evaluates the both in vivo and in vitro impact of quantum dots (QD , zinc sulphide capped cadmium selenide semiconductor nanocrystals) a fluorescent nanoparticle label with potential as an optical in vivo imaging agent. This work reviews nanoparticle characterization techniques and their importance to biological responses, and surveys QD interactions both in vivo and in vitro. We collected pharmacokinetic and toxicity data by a) quantitatively surveying the in vivo absorption, distribution , metabolism and excretion of QDs, and b) measuring the impacts of QDs on relevant organs (in vivo) and cells (in vitro). Neither of these areas had been explored when this thesis was started.
In vivo, intravenous QD dosing in Sprague-Dawley rats showed uptake into reticuloendothelial cells with surface coating dependent kinetics, slow degradation, no excretion detected in feces or urine, and no indications of toxicity. The liver took up the majority of dose after 90 minutes and small amounts of QDs appeared in the spleen, kidney, and bone marrow. After 30 days, the cadmium concentration in the kidneys increased to 3µg/g without a proportional amount of zinc, indicating QD breakdown.
In vitro we noted phagocytic capacity comparable to in vivo results, QD breakdown, and a retention of normal macrophage function thereby demonstrating that primary rat liver macrophages (Kupffer cells) are an appropriate in vitro system with which to investigate the cellular responses to quantum dots. Such an in vitro model will facilitate faster evaluation of individual nanotechnologies intended for in vivo use.
This dissertation addresses a lack of in vivo background information needed to understand the consequences of QD exposure; though QD fail to demonstrate pharmacokinetics desirable for in vivo imaging agents, they are not toxic. Importantly, we provide in vitro data that will lead to the development of accurate and efficient in vitro primary screening methods that will be central to the further development of biomedical nanotechnologies.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/26171 |
| Date | 15 February 2011 |
| Creators | Fischer, Hans Christian |
| Contributors | Chan, Warren C. W. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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