Electrochemical Generation of Reactive Species and their Application as Chemotherapeutics

Boudreau, Jordache
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University of Guelph

A major limitation in developing a successful cancer treatment is the need for a distinction between normal and cancerous tissue. For solid tumors, this distinction can be made on a spatial basis, and successful treatments have been developed accordingly; however, many of these treatments cause pathologies in healthy tissue, much to the detriment of patient health. To address this issue for solid tumours, a conceptual approach would be to administer the chemotherapeutic drug locally, such that the intra-tumour concentration was high, while the systemic exposure to the drug remained low, thus, minimizing side effects. The present research focuses on providing proof-of-concept for the electrochemical generation of a toxicant from a prodrug, and subsequent use to elicit cytotoxicity in cancer cells, in attempts to electrochemically mimic monooxygenase-catalyzed bioactivation. Electro-oxidation of acetaminophen and cyclophosphamide substrates at graphite and Ti/RuO2 anodes was successful in generating their respective toxicants; however, the graphite anode was superior with respect to current efficiency and toxicant yield. Electrolyses conducted in batch and flow reactors produced effluents which reduced EMT-6 cell viability to the IC99 level. This thesis provides proof-of-concept for electrochemical prodrug activation as a viable area for further cancer research.

electrochemistry, toxicology, cancer biology, cyclophosphamide, acetaminophen, focal therapy, graphite, oxidation, bioactivation