This projects seeks to improve the current state of photosensitization used in the detection and photodynamic therapy of neoplastic disease. Since the value of Hematoporphyrin Derative and Photofrin are well documented, this project will examine the electronic and fluorescent effects of three of the known components of HpD and Photofrin-II: protoporphyrin, hematoporphyrin, and dihematoporphyrin ether/ester. These three prophyrins will be examined by ultraviolet/visible and excitation/emission fluorescence spectrophotometry in the metal free and metallated Zinc forms. The metal free and Zinc metallated porphyrins will be examined in PBS (phosphate buffered saline; ph-7.2) free of cells and in PBS solutions containing PTK2 cells (rat kangaroo epithelial kidney cells). The respective porphyrin solutions containing the PTK2 cells will also be subjected to photoirradiation form a dye laser2 to examine the phototoxicity of the metal-free and metallated Zinc porphyrins.
The specific aims of this project are to test Zinc substituted porphyrin complexes against known components of HpD and Photofrin-II. The effects to be examined include the following: 1). identification and assignment of electronic transitions. 2). a comparison of the fluorescence lifetime and quantum yields, 3). measurements and comparisons of the photokill ratios. The comparison of HpD and Photofrin-II components against their metallated Zinc analogues is important because it is well known that metalloporphyrins are better able to fluoresce and phosphoresce than their demetallated counterparts. If it can be shown that Zinc substituted protoporphyrin, for example, exhibits a superior fluorescence than does protoporphyrin in the demetallated form, this complex could be used as a localizer for cancer cells. If any one of these Zinc-porphyrins exhibited superior sensitization of cells, they could be used as photosentizers, either as precursors for or in conjunction with HpD.
