Strategies to enhance photodynamic therapy

Abstract

Photodynamic therapy (PDT) is well-known cancer treatment modality that has been used with good results and is based on the combined use of photosensitizer, light and molecular oxygen to induce cell death. The relative in vitro efficacy of PDT with a fluorinated bacteriochlorin, that generates singlet oxygen, hydroxyl radical and superoxide ion, or with temoporfin, which only generates singlet oxygen, depends on the superoxide dismutase (SOD) activity levels of the cell lines and depends the inhibition of glycolysis. The addition of ascorbate further potentiates phototoxicity in A549 cells, presumably by electron transfer to the radical cation of the photosensitizer and consequent increase in the turnover of radicals. The inhibition of catalase and the depletion of the glutathione pool have similar effects in A549 and CT26 cells, although less impressive in CT26. CT26 cells have a higher SOD activity level and are less sensitive to Type I processes. The phototoxicity towards CT26 cells seems to be mostly mediated through singlet oxygen and the inhibition of the cell antioxidant defence system is less effective in potentiating PDT phototoxicity. Inhibition of glycolysis leads to increased steady-state levels of ROS and enhanced cell killing by oxidative stress due to 2-Deoxy-D-glucose (2-DG) inhibit the formation of pyruvate and NADPH, which function in the detoxification pathways of H2O2.