Dr. Erin Anderson, NIH/NCI
Friday, February 17, 2017 · 12 - 1 PM
“Near-IR Uncaging or Photosensitizing Dictated by Oxygen Tension”
“Photodynamic therapy (PDT) has been shown to effectively target cancer in the clinic. However, this approach relies on the generation of reactive oxygen species, and hypoxic tumor cells are resistant to treatment. The discovery of compounds with alternative photoreactiviity that is triggered by low energy near-IR light is critical to circumventing this limitation. We have designed a single molecule that acts as a photosensitizer for PDT under normoxia and then transitions to near-IR induced drug uncaging in response to reduced oxygen tension. We demonstrate that PDT active silicon phthalocyanines undergo a 690 nm light triggered silicon oxygen bond cleavage reaction selectively under hypoxic conditions. Mechanistic studies indicate that uncaging proceeds through an intermolecular photoinduced electron transfer pathway. Cellular studies confirm two distinct mechanisms of action: reactive oxygen species induced phototoxicity under normoxic conditions and small molecule release/drug action under hypoxia. Complementary mechanisms of action target each arm of this treatment to the cell population that is evaded by the other eliminating both normoxic and hypoxic tumor cells with a single agent.”