TUMOR PHOTOTHERAPY - NEW PHOTODYNAMIC SENSITIZERS

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This is a continuation application that concerns the development and characterization of a new generation of tetraazaporphyrin macrocycles that has relevance to photodynamic therapy (PDT) of tumors. The naphthalocyanine (Nc) and phthalocyanine (Pc) families are selected for this study because of their intense deep-red optical absorptions, their promising photophysical properties, and their stability and compatibility with liposome and microemulsion delivery systems. Our recent studies have demonstrated conclusively that representatives of these families are excellent tumor localizers and promote deep-red-light-induced tumor necrosis at low levels. The studies are to be conducted at a variety of levels. One component, directed by Dr. M. E. Kenney, will focus on molecular synthesis and characterization of new and developed members of the families. A second component concerning molecular photobiology will be followed at the PI's laboratory in Bowling Green. This will include a variety of photophysical evaluations in homogeneous and in microheterogeneous media in order to assess photodynamic effectiveness. Laser flash and c.w. irradiation methods will be employed. The third component, directed by Dr. G. Jori, will focus on animal-level studies on the effects of sensitizer structure and carrier vehicle on the pharmacokinetic distribution among tissues, and on the phototherapeutic effectiveness of selected photosensitizers. An interesting new question to be addressed is whether the deep-red-absorbing compounds will be effective against pigmented melanomas in mice. The three laboratories where these studies are to be carried out are all excellently equipped with the requisite facilities. The outcome of this program will be a series of new molecules about which an abundance of quantitative evidence concerning their PDT effectiveness will be accumulated. At another level this information will be highly relevant to a deeper understanding of the mechanism of photodynamic action.