Date of Final Oral Examination (Defense)

5-2011

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Biology

Department

Biology

Major Advisor

Denise Wingett, Ph.D.

Abstract

Nanoparticles (NP) are increasingly being recognized for their utility in the field of medicine, including use as drug carriers and imaging tools. We demonstrated that ZnO NP preferentially kill cancerous cells of the T cell lineage, and extended this research to evaluate other cells types, including normal and malignant B cells, and normal and malignant breast and prostate epithelial cells. Preferential ZnO nanoparticle cytotoxicity occurred for multiple types of cancer cells, but was most pronounced for non-adherent cells of hematopoietic lineage. Normal T and B lymphocytes showed the greatest resistance to NP toxicity, followed by normal breast epithelial cells, and appeared to be closely tied to cellular proliferative potential. Reactive oxygen species generation contributed, at least in part, towards cancer cell selectivity with greater levels of reactive oxygen species being induced in cancerous cells compared to normal cell counterparts. The extracellular dissolution of ZnO NP did not appear to appreciably contribute to the toxicity mechanism, and endocytosis of nanoparticles appeared to be required for toxicity. Particle charge was found to have an effect on toxicity, with more cationic nanoparticles having a greater toxicity than neutral/anionic particles, and may be an important factor in future studies aimed at improving cancer cell selectivity. Overall, these findings suggest that ZnO nanoparticles may have utility in anticancer regimens aimed at hematological malignancies.

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