LE3 .A278 2013

2013

McFarland, Sherri

Acadia University

Bachelor of Science

Honours

Biology

Biology

Cancer is a prevalent medical concern and there is much room for improvement in the drugs and therapies used to treat it. One such treatment is photodynamic therapy (PDT). PDT makes use of relatively non-toxic drugs that are activated by light to cause cell death. An ideal PDT agent will have many important qualities and should have limited toxicity in the dark but cause severe cytotoxicity upon administration of a light dose, have a mechanism of uptake into cancerous cells and/or a cancer-specific molecular target, be capable of absorbing light at long wavelengths, and be capable of biological activity in an oxygen-independent manner. Metal-based compounds can be synthesized in to meet as many of these criteria as possible. To assess the effectiveness of compounds as potential agents for PDT, a series of biological experiments is performed. Such experiments use a variety of techniques and procedures to evaluate the presence of DNA binding, light-induced damage to DNA, enzyme targeting, uptake mechanisms, as well as cytotoxicity and photocytotoxicity of each compound in two cancer cell lines. A new technique to assess the mechanism of action (necrosis vs. apoptosis) of cell death was employed to assess its value as a potential screening procedure for photodynamic compounds but was impractical. Experiments were implemented as a means for understanding the intricacies of each compound and to judge which compounds should be sent on through the resource exhaustive process of in vivo experiments, leading eventually to human clinical trials. Although each experiment provided valuable information about the compounds studied, no single experiment is a perfect indicator of good PDT action in cancer cell lines. Consequently, the in vitro work described within this thesis has aided in redirecting the drug discovery process in the McFarland laboratory.

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https://scholar.acadiau.ca/islandora/object/theses:952