Photodynamic Therapy

Development of Photodynamic Therapeutic Agents

Our primary objective in this area has been the rational development of drugs for the treatment of solid tumors and for the eradication of pathogens in whole blood. When we entered the field of photodynamic therapy (PDT), there were few systematic efforts to develop drugs from classes of compounds other than those belonging to the porphyrin family. This remains true today. Our research is based on the premise that any effort to extend and/or improve the applicability of PDT would require the use of photosensitizers that have inherently different physicochemical and pharmacological properties from the porphyrins. We chose to study the benzophenoxazine family of dyes because they possess many of the properties that characterize a good PDT agent. For example, they preferentially localize in neoplastic cells, are relatively non-toxic in the dark, absorb red light efficiently and are rapidly eliminated from the body. A key finding is that some of the novel photosensitizers we have developed inactivate tumors via a different mechanism than is operative with the porphyrins: benzophenothiazine PDT drugs, such as EtNBS, mediate the destruction of neoplasia by directly damaging intracellular organelles whereas porphyrin derivatives act by shutting down the vasculature that support tumor tissue. Thus the two approaches are complimentary and, when used simultaneously, synergistic.

In collaboration with physicians from Tufts School of Veterinary Medicine we recently demonstrated the effectiveness of the benzophenothiazine dye EtNBS against spontaneous tumors in pet cats and dogs (Clinical Cancer Research 4: 2207-2218 (1998). Below we present pre- and post-treatment photographs of Blaze, one of the successes of this study.


Before PDT

2mg/Kg EtNBS (i.v.)
650nm/25min.
200mW/cm2
2X


Two Yrs. Post Initial PDT