Date of Award

2-2-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Applied Science

First Advisor

Maurice Kleve

Abstract

Cancer bionanotechnology is an interdisciplinary area of research in applied biosciences, biomedical engineering, and nano-medicine. Currently, apoptotic cell death inducers and regulators are considered to have significant potential for cancer therapy. The ability to escape apoptosis is one of the key properties of human cancer. Pancreatic cancer that has the highest fatality rates of all cancers is prompt to evade apoptosis. Nanomaterials like Ni NWs have various novel properties that could be very useful in bio-medical applications at the molecular and cellular levels. The overall objective of this research was to investigate the antiproliferative and apoptogenic properties of Ni NWs against a pancreatic ductal adenocarcinoma cell line and compare the results with a normal cell line. In my research it was found that Ni NWs uptake and cellular internalization through endocytosis. This revealed that there were no morphological apoptotic characteristics expressed in 3T3-L1, whereas Panc-1 fully mimicked the morphological apoptotic characteristics with Ni NWs treatment when compared to the control. Analysis of FC cell cycle distribution after Ni NWs treatment showed no significant difference in DNA content and the sub-G1 fraction on normal 3T3-L1 cells as compared to the control. On the other hand, in cancerous Panc-1 cells, FC cell cycle analysis revealed that the cell cycle was arrested in the G0 / G1 phases and there was a significant increase of sub-G1 after treatment with Ni NWs. To test the hypothesis, Panc-1 cell death induced by Ni NWs occurred via the apoptotic pathway, the expression of caspase-3 during Ni NWs treated cell death was investigated. FITC intensity based FC histogram and FM revealed that the Ni NWs treated immuno-stained Panc-1 cells expressed caspase-3. In addition, FC cell cycle arrest and ROS generation revealed the PCD was indeed apoptosis. The research results indicated that Ni NWs could inhibit proliferation and induce apoptosis of Panc-1 cell line in a concentration and exposure time dependent manner. The molecular mechanisms demonstrated Ni NWs as inducers of apoptotic Panc-1 cell death, thus showing strong candidacy for targeting cell selective applications in bio-nanomedicine, especially in pancreatic cancer therapy.

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