Correlation between subcellular localization and photodynamic efficacy

A variety of agents have now been identified that can selectively sensitize neoplastic cells and other tissues to light. This review classifies a group of photosensitizers according to their initial affinity for specific sub-cellular organelles in vitro, and describes the consequences of each major localization site with regard to direct tumor cell kill. Considerations pertinent to determinants of efficacy in animal models and in clinical applications are also pointed out. One consequence of photodynamic therapy leading to cell death involves photodamage to anti-apoptotic members of the Bcl-2. These proteins are located on the endoplasmic reticulum and mitochondrial membranes. Direct mitochondrial photodamage can also initiate apoptosis. Agents that target lysosomes can bring about apoptotic death via an indirect route, but this does not appear to limit their usefulness. Agents that target the plasma membrane can re-localize to the cytosol during irradiation and cause photodamage to elements of the apoptotic process, resulting in necrosis. Implications of these findings are discussed. Copyright (c) 2004 Society of Porphyrins & Phthalocyanines.