Merocyanine 540 was found to be an efficient and selective sensitizer for dyemediated photoinactivation of a broad range of neoplastic cells. The mechanism by which the photodynamic action occurs is yet very poorly understood. the only study available indicates an involvement of singlet oxygen. However, my recent work has shown that merocyanine 540 has, in contrast to most photosensitizers used, an extremely low triplet and singlet oxygen quantum yield in solution as well as in biomimetic systems. These results clearly indicate that the high efficiency in cell inactivation by merocyanine 540 cannot solely be attributed to a Type II mechanism involving singlet oxygen. IN this project I propose to investigate the mechanism of photodynamic action of cyanine dyes simultaneously in solution, biomimetic systems and in different types of neoplastic cells. The study will include the determination of singlet oxygen quantum yields in solution and in microheterogeneous media, and experiments will be designed to correlate singlet oxygen quantum yields and cell photoinactivation. Type I mechanisms will be investigated by studying the formation of superoxide and the electron-transfer reaction between cyanine dyes and possible membrane components. Since cyanines are photobleached when incorporated into cells, the photoproducts in biomimetic systems and in cells will be isolated, characterized, compared and tested for cell toxicity. The mechanisms involved in cell photoinactivation. Finally, the results from these investigations will be used to design new and efficient photosensitizers with absorption maxima above 650 nm, a wavelength region where light is able to penetrate the tissue.
