Design and evaluation of DNA photocleaving agents for bioinorganic applications

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DNA photocleaving agents are molecules capable of inducing single- or double-strand breaks in the DNA backbone. Molecules that cleave DNA upon activation with light are of significant interest for use in photodynamic therapy (PDT), a strategy that has been applied to the successful treatment of certain cancers, intravascular disease, and age-related macular degeneration. Briefly, PDT employs an organic photosensitizer that generates toxic oxygen species upon irradition with visible light. Unfortunately, organic photosensitizers rely on the presence of oxygen to function and cannot be activated by wavelengths of light where tissue is most transparent. Therefore, PDT is not effective in treating deep or hypoxic tissue, which comprises some of the most malignant and drug-resistant tumours. This proposal outlines a research plan that is devoted to overcoming such limitations by introducing transition metal complexes as photosensitizers for inorganic PDT. This proposal will identify inorganic systems that damage DNA when activated by near-IR light and do not require oxygen to function. Since DNA is the blueprint for all cellular function, new photosensitizers that target the genetic machinery will elicit maximal damage in a pre-selected area.