| dc.description.abstract | Cancer is one of the leading causes of death in the United States and is predicted to directly affect 38% of the population over the course of their life. Cancer is categorized as a collection of diseases primarily characterized by aberrant cellular proliferation. Many current cancer therapies, such as chemotherapy lack the ability to differentiate between cancer cells and normal cells resulting in several negative side effects. To minimize these side effects, there has been a huge push to develop targeted therapies, which exploit cancer-specific features to exhibit selective toxicity towards cancer cells. Due to their high proliferative and metabolic rate, some cancers overexpress vitamin receptors such as the biotin receptor. Biotin, also known as vitamin B7, functions intracellularly as an important coenzyme for several carboxylase enzymes involved in fatty acid synthesis, amino acid metabolism and gluconeogenesis. Thus, by overexpressing the biotin receptor some cancers increase their overall absorption of biotin resulting in a higher metabolic and proliferation rate. Furthermore, the high metabolic rate in cancer leads these cells to have increased susceptibility to damage by reactive oxygen species (ROS) which can trigger apoptosis at high intracellular levels. Ferrocene is an organometallic compound with an iron-center that has been shown to generate ROS in cancer cells. Therefore, our project is exploring this overexpression of the biotin receptor as a potential avenue for targeted therapy against several cancers. Since certain cancers overexpress the biotin receptor and absorb biotin with a higher efficiency, we hypothesize that conjugating biotin to ferrocene will increase the efficiency of ferrocene entering cancer cells, resulting in selective toxicity. Therefore, we have produced a library of biotin-ferrocene conjugates to test their ability to selectively enter cancer cells and generate ROS. Experiments were conducted utilizing ferrocene and a variety of conjugates (C1, C2, C3, 2) in both cancer (MCF-7) and non-cancer cells (HEK293). | |
