ABSTRACT

Photodynamic therapy (PDT) is the use of drugs (photosensitizers) that are activated by light, generating photoproducts that kill cells in the presence of oxygen. While the basic concept is over a century old, its development was significantly accelerated by the availability of lasers and other practical high-brightness light sources, optical fibres enabling the delivery of the light to many sites within the body and the synthesis of photosensitizers with high photo-physicalefficiency, good bio-distribution and disease targeting, and different biological mechanisms of action. For most photosensitizers currently in clinical use or under investigation, the active photoproduct is believed to be mainly an excited singlet state of molecular oxygen (1O2) that is generated by the photophysical process illustrated in figure D3.2.3.1. In this process, the photosensitizer returns to its ground state after energy transfer to oxygen and can be re-activated. Thus, it acts essentially as a catalyst for oxygen activation. The 1O2 damages tissue/cell components, primarily membranes, through lipid peroxidation, leading to cell death or altered function. Particularly in a low-oxygen environment, other processes, such as interactions of the excited singlet or triplet-state molecule with biomolecules, may also contribute to the overall photobiological effect. Absorption (activation) spectra for typical PDT photosensitizers are shown in figure D3.2.3.2.