Janusz M. Dabrowski

Mechanisms of Singlet‐Oxygen and Superoxide‐Ion Generation by Porphyrins and Bacteriochlorins and their Implications in Photodynamic Therapy

New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction.

Pro-oxidant and Antioxidant Effects in Photodynamic Therapy: Cells Recognise that Not All Exogenous ROS Are Alike

Photodynamic therapy (PDT) uses light, photosensitizer molecules and oxygen to generate reactive oxygen species (ROS) that kill cancer cells. Redaporfin, a new photosensitizer in clinical trials, generates both singlet oxygen and superoxide ions. We report the potentiation of redaporfin–PDT in combination with ascorbate and with the inhibition of antioxidant enzymes in A549 (human lung adenocarcinoma) and CT26 (mouse colon adenocarcinoma) cells. The addition of ascorbate and the inhibition of superoxide dismutase (SOD) strongly increased the phototoxicity of redaporfin towards A549 cells but not towards CT26 cells. The inhibition of catalase and the depletion of the glutathione pool also potentiate redaporfin–PDT towards A549 cells. The lower SOD activity of A549 cells might explain this difference. SOD activity levels may be explored to increase the selectivity and efficacy of PDT with photosensitizers that generate radical species.