Molecular damage

Photodynamic therapy (PDT) rapidly produces large amounts of reactive oxygen species (ROS) to induce death of photosensitized cells. As previously described in Chap. 2, excited photosensitizer (PS) molecules can either donate electrons (type 1) or energy (type 2) to ground-state oxygen to produce superoxide radicals (O₂^•-) or singlet oxygen (¹O₂). Each type of ROS has characteristic chemical reactivity and reacts with different types of chemical bonds present in biomolecules and, consequently, will lead to different types of cell damage. Once again, what determines the mechanism of cell death directly depends on both: the PS localization site within the cell and total extent of oxidative stress produced during therapy (i.e., light dosimetry and efficiency of ROS generation). To elucidate the mechanisms of photooxidative damage and the consequent biological effects, this chapter will cover the most relevant chemical reactions related to oxidative damage caused by ¹O₂ and free radicals. Photodynamic therapy (PDT) quickly generates large amounts of reactive oxygen species (ROS) to induce death of photosensitized cells. If such excessive amount of ROS could be found occurring naturally in living systems, it would indeed represent some severe pathological condition. As previously described in Chap. 2, excited photosensitizer (PS) molecules can donate either electrons (type 1) or energy (type 2) to ground-state oxygen to produce superoxide radicals (O_2•-) or singlet oxygen (¹O₂). Each type of ROS has characteristic chemical reactivity toward different chemical bonds present in biomolecules and, consequently, will lead to different types of cell damage. In this chapter we discuss the most relevant chemical reactions related to oxidative damage caused by photodynamic reactions to clarify the mechanisms of molecular damage caused by PDT.