A Role For Reactive Oxygen Species In Photodynamic Therapy

A ROLE FOR REACTIVE OXYGEN SPECIES IN PHOTODYNAMIC THERAPYbyMICHAEL PRICEDecember 2012Advisor:David Kessel, Ph.D.Major:Cancer BiologyDegree:Doctor of PhilosophyPhotodynamic therapy (PDT) is based on the ability of certain photosensitizingagents to selectively localize in neoplastic cells and their vasculature. Subsequentirradiation at a wavelength corresponding to a photosensitizer absorbance band excitesthe photosensitizer molecules, leading to energy transfer reactions and fluorescence. Itwas initially concluded that the phototoxic effect occurred when energy from the excitedstate of the photosensitizer was transferred to dissolved oxygen to form singlet oxygen.This product has a very brief half-life and will cause cellular damage only in theimmediate vicinity of its formation. But an excited-state photosensitizer can also interactwith oxygen to form superoxide anion radical, which in turn (through the action ofsuperoxide dismutase) is converted to hydrogen peroxide and hydroxyl radical via theFenton reaction. These reactive oxygen species (ROS) all posses properties (i.e.lifetime, reactivity and diffusion distances) that make them at least as cytotoxic assinglet oxygen. The hypothesis examined in this dissertation was that the particularreactive oxygen species being formed might be an important determinant ofphotodynamic therapy efficacy.Initial studies were designed to assess specificity of several commercially