Cellular damage

Classical pharmacology is normally concerned with defined molecular structures that can bind to specific proteins and either inhibit or enhance the protein function to achieve some biological response with therapeutic benefit. In photodynamic therapy (PDT) context, we rarely rely on such target specificity to achieve therapeutic success. Although some recent photosensitizers have been functionalized with target-specific molecules, such as antibodies, to recognize specific cells and enhance therapy specificity, ROS produced inside the cell will damage all susceptible molecules within the diffusion radius. According to the previous chapter, both hydroxyl radicals and singlet oxygen are highly reactive toward most of the abundant biological molecules contained in cells. In this chapter we discuss how such capacity of PDT to provoke multiple sites of molecular damages in the cellular context is associated with the phototoxicity produced. Also, we discuss how cellular antioxidant and xenobiotic defenses can influence on cellular tolerance against photodynamic inactivation.