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Zinc octa-n-alkyl phthalocyanines in photodynamic therapy: photophysical properties, accumulation and apoptosis in cell cultures, studies in erythrocytes and topical application to Balb/c mice skin

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Abstract

Two octa-substituted phthalocyanines, namely 1,4,8,11,15,18,22,25-octakis(decyl)phthalocyaninato zinc(ii) (ZnODPc) and 1,4,8,11,15,18,22,25-octakis(pentyl)phthalocyaninato zinc(ii) (ZnOPPc), were investigated for their use in photodynamic therapy (PDT) after topical application. Both substances exhibited favourable properties as photosensitisers in vitro: absorption maxima around 700 nm with absorption coefficients of about 190000 (M−1 cm−1), a singlet oxygen quantum yield of 0.47 ± 0.02 (ZnODPc), and good accumulation in keratinocytes and fibroblasts. Cell death after phthalocyanine-photosensitisation appeared to occur mainly via apoptosis. The in vivo experiments demonstrated a good accumulation of the phthalocyanines after topical application in a tetrahydrofuran–azone formulation onto the dorsal skin of Balb/c mice: [(4.6–4.7) ± 1.0]% of deposited dye could be recovered after 3 h from deposition. ZnODPc showed significantly better skin-photosensitising properties than ZnOPPc and is therefore a potential candidate for the treatment of psoriasis.

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References

  1. T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan and Q. Peng, Photodynamic Therapy, J. Nat. Cancer Inst., 1998, 90, 889–905.

    Article  CAS  Google Scholar 

  2. L. Kaestner, Tetraphenylporphyrine–Farbstoffe für die photodynamische Therapie, Logos Verlag, Berlin, 1997.

    Google Scholar 

  3. S. Murugesan, S. Shetty, T. Srivastava, A. Samuel and O. Noronha, Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors, J. Photochem. Photobiol. B, 2002, 68, 33.

    Article  CAS  Google Scholar 

  4. K. Kassab, C. Fabris, M. P. Defilippis, D. Dei, L. Fantetti, G. Roncucci, E. Reddi and G. Jori, Skin-photosensitizing properties of Zn(II)-2(3), 9(10), 16(17), 23(24)-tetrakis-(4-oxy-N-methylpiperidinyl) phthalocyanine topically administered to mice, J. Photochem. Photobiol. B, 2000, 55, 128–137.

    Article  CAS  Google Scholar 

  5. B. Henderson and T. J. Dougherty, How does photodynamic therapy work?, Photochem. Photobiol., 1992, 55, 145–157.

    Article  CAS  Google Scholar 

  6. J. Moan and K. Berg, Photochemotherapy of cancer: Experimental research, Photochem. Photobiol., 1992, 55, 931–948.

    Article  CAS  Google Scholar 

  7. L. Milgrom and A. J. MacRobert, Light years ahead (Review), Chem. Br., 1998, 34, 45–50.

    CAS  Google Scholar 

  8. I. Rosenthal and E. Ben-Hur, Phthalocyanines in Photobiology, in Phthalocyanines, Properties and Applications, ed. C. C. Leznoff and A. B. P. Lever, VCH Publishers, Berlin, 1989.

    Google Scholar 

  9. C. Fabris, G. Valduga, G. Miotto, L. Borsetto, G. Jori, S. Garbisa and E. Reddi, Photosensitization with zinc (II) phthalocyanine as a switch in the decision between apoptosis and necrosis, Cancer Res., 2001, 61, 7495–7500.

    CAS  PubMed  Google Scholar 

  10. D. J. Ball, S. Mayhew, S. R. Wood, J. Griffiths, D. I. Vernon and S. B. Brow, A comparative study of the cellular uptake and photodynamic efficacy of three novel zinc phthalocyanines of differing charge, Photochem. Photobiol., 1999, 69, 390–396.

    Article  CAS  Google Scholar 

  11. D. J. Ball, S. R. Wood, D. I. Vernon, J. Griffiths, T. M. Dubbelman and S. B. Brown, The characterisation of three substituted zinc phthalocyanines of differing charge for use in photodynamic therapy. A comparative study of their aggregation and photosensitising ability in relation to mTHPC and polyhaematoporphyrin, J. Photochem. Photobiol. B, 1998, 45, 28–35.

    Article  CAS  Google Scholar 

  12. J. C. Bremner, S. R. Wood, J. K. Bradley, J. Griffiths, G. E. Adams and S. B. Brown, 31P magnetic resonance spectroscopy as a predictor of efficacy in photodynamic therapy using differently charged zinc phthalocyanines, Br. J. Cancer, 1999, 81, 616–621.

    Article  CAS  Google Scholar 

  13. A. Visona, A. Angelini, S. Gobbo, A. Bonanome, G. Thiene, A. Pagnan, D. Tonello, E. Bonandini and G. Jori, Local photodynamic therapy with Zn(II)-phthalocyanine in an experimental model of intimal hyperplasia, J. Photochem. Photobiol. B, 2000, 57, 94–101.

    Article  CAS  Google Scholar 

  14. M. J. Cook, I. Chambrier, S. J. Cracknell, D. A. Mayes and D. A. Russell, Octa-alkyl zinc phthalocyanines: potential photosensitizers for use in the photodynamic therapy of cancer, Photochem. Photobiol., 1995, 62, 542–554.

    Article  CAS  Google Scholar 

  15. C. Ometto, C. Fabris, C. Milanesi, G. Jori, M. J. Cook and D. A. Russell, Tumour-localising and -photosensitising properties of a novel zinc(II) octadecylphthalocyanine, Br. J. Cancer, 1996, 74, 1891–1899.

    Article  CAS  Google Scholar 

  16. C. Fabris, C. Ometto, C. Milanesi, G. Jori, M. J. Cook and D. A. Russell, Tumour-localizing and tumour-photosensitizing properties of zinc(II)-octapentyl-phthalocyanine, J. Photochem. Photobiol. B, 1997, 39, 279–284.

    Article  CAS  Google Scholar 

  17. J. D. Spikes and J. C. Bommer, Photosensitizing properties of mono-L-aspartyl chlorin e6 (NPe6): a candidate sensitizer for the photodynamic therapy of tumors, J. Photochem. Photobiol. B, 1993, 17, 135–143.

    Article  CAS  Google Scholar 

  18. E. Gandin, Y. Lion, A. Van de Vorst, Production of radicals by singlet oxygen reaction: an E.S.R. study, Arch. Int. Physiol. Biochim., 1979, 87, 1046–1047.

    CAS  PubMed  Google Scholar 

  19. J. R. Lakowicz, Principles of Fluorescence Spectroscopy, Plenum Press, New York, 1983.

    Book  Google Scholar 

  20. G. Valduga, G. Bianco, G. Csik, E. Reddi, L. Masiero, S. Garbisa and G. Jori, Interaction of hydro- or lipophilic phthalocyanines with cells of different metastatic potential, Biochem. Pharmacol., 1996, 51, 585–590.

    Article  CAS  Google Scholar 

  21. H. A. Crissman and J. A. Steinkamp, A new method for rapid and sensitive detection of bromodeoxyuridine in DNA-replicating cells, Exp. Cell Res., 1987, 173, 256–261.

    Article  CAS  Google Scholar 

  22. D. Jocham, Clinical experiences and expectations in Photodynamic tumor therapy. 2nd and 3rdGeneration Photosensitizers, ed. J. G. Moser, Harwood Academic Publishers, Amsterdam, 1998, pp. 213–225.

    Google Scholar 

  23. G. Jori and C. Fabris, Relative contributions of apoptosis and random necrosis in tumour response to photodynamic therapy: effect of the chemical structure of Zn(II)-phthalocyanines, J. Photochem. Photobiol. B, 1998, 43, 181–185.

    Article  CAS  Google Scholar 

  24. N. L. Oleinick, A. R. Antunez, M. E. Clay, B. D. Rihter and M. E. Kenney, New Phthalocyanine Photosensitizers for Photodynamic Therapy, Photochem. Photobiol., 1993, 57, 242–247.

    Article  CAS  Google Scholar 

  25. J. He, H. E. Larkin, Y.-S. Li, B. D. Rihter, S. I. A. Zaidi, M. A. J. Rodgers, H. Mukhtar, M. E. Kenney and N. L. Oleinick, The Synthesis, Photophysical and Photobiological Properties and in vitro Structure-Activity Relationships of a Set of Silicon Phthalocyanine PDT Photosensitizers, Photochem. Photobiol., 1997, 65, 581–586.

    Article  CAS  Google Scholar 

  26. C. Y. Anderson, K. Freye, K. A. Tubesing, Y.-S. Li, M. E. Kenney, H. Mukhtar and C. A. Elmets, A Comparative Analysis of Silicon Phthalocyanine Photosensitizers for in vivo Photodynamic Therapy of RIF-1 Tumors in C3H Mice, Photochem. Photobiol., 1998, 67, 332–336.

    Article  CAS  Google Scholar 

  27. S. Gupta, N. Ahmad and H. Mukhtar, Involvement of Nitric Oxide during Phthalocyanine (Pc 4) Photodynamic Therapy-mediated Apoptosis, Cancer Res., 1998, 58, 1785–1788.

    CAS  PubMed  Google Scholar 

  28. A. C. E. Moor, A. E. Wagenaars-van Gompel, A. Brand, T. M. A. R. Dubbelman and J. VanStevenick, Primary Targets for Photoinactivation of Vesicular Stomatitis Virus by AlPcS4 or Pc4 and Red Light, Photochem. Photobiol., 1997, 65, 465–470.

    Article  CAS  Google Scholar 

  29. X. J. Zhao, S. Lustigman, Y. S. Li, M. E. Kenney, E. Ben-Hur, Structure-Activity and Mechanism Studies on Silicon Phthalocyanines with Plasmodium falciparum in the Dark and Under Red Light, Photochem. Photobiol., 1997, 66, 282–287.

    Article  CAS  Google Scholar 

  30. E. Ben-Hur, W. S. Chan, Z. Yim, M. M. Zuk, V. Dayal, N. Roth, E. Heldman, A. Lazo, C. R. Valeri and B. Horowitz, Photochemical Decontamination of Red Cell Concentrates with the Silicon Phthalocyanine Pc 4 and Red Light, Dev. Biol., 1999, 102, 149–155.

    Google Scholar 

  31. E. Ben-Hur, M. M. Zuk, J. Oetjen, W.-S. Chan, L. Lenny and B. Horowitz, Photochemical Decontamination of Red Cell Concentrates with the Silicon Phthalocyanine Pc 4 and Red Light, J. Biomed. Optics, 1999, 4, 292–297.

    Article  CAS  Google Scholar 

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Author notes

  1. Lars Kaestner

    Present address: Institute of Molecular Cell Biology, Faculty of Medicine, Saarland University, 66421, Homburg, Germany

Authors and Affiliations

  1. Gentian AS, Belsetsvingen 39, 1348, Rykkinn, Norway

    Lars Kaestner & Paul D. Edminson

  2. Norwegian Radiation Protection Authority, Department of Radiation Medicine, P.O. Box 55, 1332, Østerås, Norway

    Lars Kaestner & Terje Christensen

  3. Department of Biology, University of Padua, Via U. Bassi 58/B, 35131, Padova, Italy

    Mara Cesson, Kawser Kassab & Giulio Jori

  4. School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, Norfolk, UK, NR4 7TJ

    Michael J. Cook & Isabelle Chambrier

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  1. Lars Kaestner
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Correspondence to Lars Kaestner.

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Kaestner, L., Cesson, M., Kassab, K. et al. Zinc octa-n-alkyl phthalocyanines in photodynamic therapy: photophysical properties, accumulation and apoptosis in cell cultures, studies in erythrocytes and topical application to Balb/c mice skin. Photochem Photobiol Sci 2, 660–667 (2003). https://doi.org/10.1039/b211348a

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