Reactive Oxygen Species in Photodynamic Therapy: Mechanisms of Their Generation and Potentiation

Reactive oxygen species (ROS) play key roles in cell signaling systems and homeostasis, and they are also fundamental to photodynamic therapy (PDT). PDT efficacy can be affected by the nature and persistence of ROS. A comprehensive understanding of ROS generation pathways greatly facilitates the analysis of photodynamic mechanisms and enables potentiation of PDT efficacy. Diverse methods exist to distinguish between Type I and Type II mechanisms of ROS generation. The direct monitoring of O-1(2) formation involves the detection of its phosphorescence at 1270 nm. Electron spin resonance is also used in conjunction with appropriate spin traps for detection of oxygen-centered radical species. Moreover, a variety of more or less specific fluorescent probes are frequently used to detect both singlet oxygen and free radicals. This chapter summarizes our recent efforts in the design and characterization of new ROS-generating systems for PDT. Special attention is given to bacteriochlorins because they absorb in the NIR, generate ROS via both Type I and Type II mechanisms, and are very efficient in the PDT treatment of several types of tumors including pigmented melanoma. The current status and possible opportunities of ROS generation and potentiation in PDT are highlighted. Particular emphasis is placed on the elucidation of the ROS-mediated photochemical and molecular mechanisms that give rise to the establishment of PDT as a first-line systemic treatment of highly resistant diseases, especially invasive and metastatic tumors.