Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review

Reactive oxygen species (ROS) are constantly generated and eliminated in the biological system, and play important roles in a variety of normal biochemical functions and abnormal pathological processes. Growing evidence suggests that cancer cells exhibit increased intrinsic ROS stress, due in part to oncogenic stimulation, increased metabolic activity, and mitochondrial malfunction. Since the mitochondrial respiratory chain (electron transport complexes) is a major source of ROS generation in the cells, the vulnerability of the mitochondrial DNA to ROS-mediated damage appears to be a mechanism to amplify ROS stress in cancer cells. The escalated ROS generation in cancer cells serves as an endogenous source of DNA-damaging agents that promote genetic instability and development of drug resistance. Malfunction of mitochondria also alters cellular apoptotic response to anticancer agents. Despite the negative impacts of increased ROS in cancer cells, it is possible to exploit this biochemical feature and develop novel therapeutic strategies to preferentially kill cancer cells through ROS-mediated mechanisms. This article reviews ROS stress in cancer cells, its underlying mechanisms and relationship with mitochondrial malfunction and alteration in drug sensitivity, and suggests new therapeutic strategies that take advantage of increased ROS in cancer cells to enhance therapeutic activity and selectivity.

In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in developing PDT agents, and (iv) the various synthetic strategies designed at the Roswell Park Cancer Institute, Buffalo, for developing highly effective long-wavelength PDT agents and their utility in constructing the conjugates with tumor-imaging and therapeutic potential (Theranostics). The clinical status of certain selected PDT agents is also summarized (205 references).