Photodynamic therapy (PDT) of neoplastic disease is a new modality currently undergoing intensive study. The major limitations of PDT are persistent skin photosensization, along with the need for irradiation at 630 nm, a wavelength difficult to achieve by laser technology. This study is designed to examine new photosensitizing dyes based on the dimeric structure which contributes to the tumor-localization by HPD, the current clinical sensitizer, but with alterations designed to promote absorbance at wavelengths greater than 750 nm. These agents will be prepared and chemically characterized by Dr. C.K. Chang. Evaluation of toxicity and of sites of photodynamic action will be carried out by Dr. Henderson. A delineation between direct tumor kill vs. indirect toxicity via vascular damage will be made. Determinants of PDT effectiveness will be determined in vivo and in vitro. We will characterize dye aggregation, hydrophobicity, affinity for different plasma macro- molecules, environmental properties of dye-binding sites and the nature of photodamage. The distribution of sensitizers among plasma protein and lipoproteins will be examined by density-gradient ultracentrifugation, with fluorescence, absorbance and (where feasible) radioactivity used to quantitate dye concentration. As the relative effectiveness of new dyes becomes established, we should be able to identify properties of these agents that predict for superior localizing and photosensitizing behavior. Exploration of these structure-activity relationships is expected to facilitate the design of new dyes for photodynamic therapy. An understanding of the determinants of selective localization and photosensitization will represent a useful contribution to our knowledge of tumor cell biology.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Experimental Therapeutics Subcommittee 1 (ET)
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Wayne State University
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Kessel, David (2018) Apoptosis, Paraptosis and Autophagy: Death and Survival Pathways Associated with Photodynamic Therapy. Photochem Photobiol :
Kessel, David; Reiners Jr, John J (2017) Effects of Combined Lysosomal and Mitochondrial Photodamage in a Non-small-Cell Lung Cancer Cell Line: The Role of Paraptosis. Photochem Photobiol 93:1502-1508
Kessel, David (2017) Subcellular Targeting as a Determinant of the Efficacy of Photodynamic Therapy. Photochem Photobiol 93:609-612
Kessel, David (2016) Photodynamic therapy: Promotion of efficacy by a sequential protocol. J Porphyr Phthalocyanines 20:302-306
Kessel, David; Evans, Conor L (2016) Promotion of Proapoptotic Signals by Lysosomal Photodamage: Mechanistic Aspects and Influence of Autophagy. Photochem Photobiol 92:620-3
Kessel, David (2015) Apoptosis and associated phenomena as a determinants of the efficacy of photodynamic therapy. Photochem Photobiol Sci 14:1397-402
Aggarwal, Neha; Santiago, Ann Marie; Kessel, David et al. (2015) Photodynamic therapy as an effective therapeutic approach in MAME models of inflammatory breast cancer. Breast Cancer Res Treat 154:251-62
Kessel, David (2015) Autophagic death probed by photodynamic therapy. Autophagy 11:1941-3
Gibbs, Jaime H; Zhou, Zehua; Kessel, David et al. (2015) Synthesis, spectroscopic, and in vitro investigations of 2,6-diiodo-BODIPYs with PDT and bioimaging applications. J Photochem Photobiol B 145:35-47
Kessel, David; Reiners Jr, John J (2015) Promotion of Proapoptotic Signals by Lysosomal Photodamage. Photochem Photobiol 91:931-6

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