Developing Activatable Photosensitizers for Fluorescence-Guided Photodynamic Therapy

Photodynamic therapy (PDT) is increasingly being recognized as an attractive alternative to conventional forms of cancer therapies. Already clinically approved, this procedure is minimally invasive; by combining light, a small-molecule photosensitizer (PS), and molecular oxygen, reactive oxygen species can be produced in situ, causing damage to vital cellular components. Subsequently, cell death occurs by apoptosis or necrosis. In practice, after a PS has been administered, an appropriate wavelength of light is irradiated at tumors and surrounding tissue. However, since PSs lack selectivity and non-specifically localize, light irradiation also destroys neighboring healthy cells. To this regard, I developed activatable-PSs that extend beyond the conventional two-layered selectivity inherent to PDT by including biomarker-specific activation with enzymes: Glutathione S-Transferase, Carboxylesterase 2, and Azoreductase. With this heightened control, these PDT beacons will give a highly specific and localized therapeutic response by unquenching the probe to restore the PS’s native properties at the target site.