Basic Reflections on Photodynamic Therapy

Abstract

Photodynamic therapy photosensitizers are now classified into several generations depending on a number of factors, the top among which is their position in the photosensitizer and photodynamic therapy developmental timeline and milestones. Although the generational development of photosensitizers was first used to mark various milestone improvements in photodynamic therapy, it became diffuse after the description of third-generation photosensitizers. The technology that emerged around the 1950s as a simple application of the photosensitizer to generate oxygen-based tissue toxicity has now become one of the leading alternatives to cancer and antimicrobial therapy. Among the first photosensitizers to be licensed was Photofrin, now termed the first generation. A proposal of photosensitizer classification into five generations is presented in this chapter. The discussion of the mechanism of photodynamic therapy, which was introduced in Chapter 1, was described with the aid of a Jablonski diagram, showing the generation of reactive oxygen species, which is due to the interaction of the triplet-state photosensitizer with oxygen molecules present in the disease site in the triplet state. Excitation of the photosensitizer to its singlet excited state leads to photosensitization of oxygen present in the disease site in the triplet state after intersystem crossing to produce toxic reactive oxygen species, which cause irreversible cell damage. Photosensitizer development for photodynamic therapy generally follows a trajectory that commences with chemical synthesis, incorporation into nanomaterials, in vitro and in vivo studies, clinical trials and clinical case studies. A wide variety of innovations now in clinical applications of photodynamic therapy are based on photosensitizers that went through this trajectory.