ABSTRACT
Photodynamic therapy (PDT) exploits the biological consequences of localized oxidative damage inicted by photodynamic processes. A schematic outline of the major steps that lead to tumor destruction by PDT is given in Figure 1.1. ree critical elements are required for the initial photodynamic processes to occur: a drug that can be activated by a photosensitizer, light, and oxygen. Interaction of light at the appropriate wavelength with a photosensitizer produces an excited triplet state photosensitizer that can interact with ground state oxygen via two dierent pathways, designated as type I and type II. e individual steps of these pathways are shown in Figure 1.2. e type II reaction that gives rise to singlet oxygen (1O2) is believed to be the dominant pathway since the elimination of oxygen or scavenging of 1O2 from the system essentially eliminates the cytocidal eects of PDT.1-3 Type I reactions, however, may become important under hypoxic conditions or where photosensitizers are highly concentrated.1 e highly reactive 1O2 has a short lifetime (<0.04 μs) in the biological milieu and therefore a short radius of action (<0.02 μm).4 Consequently, 1O2-mediated oxidative damage will occur in the immediate vicinity of the subcellular site of photosensitizer localization. Depending on photosensitizer pharmacokinetics, these sites can be varied and numerous, resulting in a large and complex array of cellular eects. Similarly, on a tissue level, tumor cells as well as various normal cells can take up photosensitizer, which, upon activation by light, can lead to eects upon such targets as the tumor cells, the tumor and normal microvasculature, and the inammatory and immune host system. PDT eects
1.1 Introduction ..........................................................................................3 1.2 Subcellular Targets for Photosensitization .......................................5 1.3 Pathways to Cell Death and Survival ................................................7 1.4 Tissue Targets of Photosensitization .................................................9
