ABSTRACT

One component of a new therapy will most likely involve development of new photosensitizers, another may embody different therapeutic protocols. Just as single-agent chemotherapies have generally been replaced by combination therapies, multisensitizer PDT protocols and combination effects that enhance the consequences of light-induced damage may play an increasing role in this field. The charge on a photosensitizing molecule plays an important role in its biological properties, and photosensitizers can be divided into two broad classes on the basis of their charge. Photodynamic therapy is characterized by a “photodynamic threshold dose”, with a well-defined threshold and steep slope of dose-response curves in vitro, and by sharp zones of necrosis in vivo. Photosensitizers that employ oxygen-dependent photochemistry will work poorly in tumor zones that are hypoxic or poorly perfused where the cells subsist primarily on glycolysis. Photodynamic therapy has been effective for many malignancies that are accessible to light, although improvements are necessary in therapeutic ratio as well as in efficacy.