Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046281-06
Application #
2092101
Study Section
Radiation Study Section (RAD)
Project Start
1988-09-01
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Bowling Green State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
617407325
City
Bowling Green
State
OH
Country
United States
Zip Code
43403

  Publications

Aoudia, M; Guliaev, A B; Leontis, N B et al. (2000) Self-assembled complexes of oligopeptides and metalloporphyrins: measurements of the reorganization and electronic interaction energies for photoinduced electron-transfer reactions. Biophys Chem 83:121-40
Zuk, M M; Rihter, B D; Kenney, M E et al. (1994) Pharmacokinetic and tissue distribution studies of the photosensitizer bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) in normal and tumor-bearing rats. Photochem Photobiol 59:66-72
Biolo, R; Jori, G; Soncin, M et al. (1994) Photodynamic therapy of B16 pigmented melanoma with liposome-delivered Si(IV)-naphthalocyanine. Photochem Photobiol 59:362-5
Rodgers, M A (1993) Reflections on type I photodynamic damage. J Photochem Photobiol B 18:296-8
Oleinick, N L; Antunez, A R; Clay, M E et al. (1993) New phthalocyanine photosensitizers for photodynamic therapy. Photochem Photobiol 57:242-7
Bellemo, C; Jori, G; Rihter, B D et al. (1992) Si(IV)-naphthalocyanine: modulation of its pharmacokinetic properties through the use of hydrophilic axial ligands. Cancer Lett 65:145-50
Rihter, B D; Bohorquez, M D; Rodgers, M A et al. (1992) Two new sterically hindered phthalocyanines: synthetic and photodynamic aspects. Photochem Photobiol 55:677-80
Zuk, M M; Rihter, B D; Kenney, M E et al. (1991) Photosensitizers for tumor therapy: determination of bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) in rat tissue and serum by high-performance liquid chromatography. J Chromatogr 568:437-44
Cuomo, V; Jori, G; Rihter, B et al. (1991) Tumour-localising and -photosensitizing properties of liposome-delivered Ge(IV)-octabutoxy-phthalocyanine. Br J Cancer 64:93-5
Cuomo, V; Jori, G; Rihter, B et al. (1990) Liposome-delivered Si(IV)-naphthalocyanine as a photodynamic sensitiser for experimental tumours: pharmacokinetic and phototherapeutic studies. Br J Cancer 62:966-70

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