Photodynamic Therapy Using Novel Zinc Phthalocyanine Derivatives and a Diode Laser for Superficial Tumors in Experimental Animals

Abstract

Photodynamictherapy (PDT) using a photo sensitizing agent and several light sources has been shown to have nonspecific and noninvasive effects on superficial cancers. Phthalocyanine (Pc) derivatives as novel photosensitizers, trifluoroethoxy-coatedzinc Pcconjugated with β-cyclodextrin (βCD-4TFEO-Pc) was synthesized and its photodynamic effect in vitro and in vivo was evaluated. βCD-4TFEO-Pc alone was completely non-cytotoxic even at high concentrations, and showed excellentphotodynamic effects in B16-F10 and HT-1080 celllines. The in vivo antitumor effect of βCD-4TFEO-Pc against B16-F10 cells transplanted on to the chorioallantoic membranes of chickembryos was 52.7%, but that of laserirradiation alone and photosensitizer alone was <7% at thedose of 50 μg pereggand 100 J/cm2 (50 mW). These data suggest that βCD-4TFEO-Pc is a useful photosensitizer for the treatment of superficial cancers. If a high-power LED with optimal wavelength is developed, excellent treatment of superficial cancers could be achieved by applying βCD-4TFEO-Pc for PDT.

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Obata, T. , Mori, S. , Suzuki, Y. , Kashiwagi, T. , Tokunaga, E. , Shibata, N. and Tanaka, M. (2015) Photodynamic Therapy Using Novel Zinc Phthalocyanine Derivatives and a Diode Laser for Superficial Tumors in Experimental Animals. Journal of Cancer Therapy, 6, 53-61. doi: 10.4236/jct.2015.61008.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Anand, S., Ortel, B.J., Pereira, S.P., Hasan, T. and Maytin, E.V. (2012) Biomodulatory Approaches to Photodynamic Therapy for Solid Tumors. Cancer Letters, 326, 8-16.
http://dx.doi.org/10.1016/j.canlet.2012.07.026
[2] Baldea, I. and Filip, A.G. (2012) Photodynamic Therapy in Melanoma—An Update. Journal of Physiology and Pharmacology, 63, 109-118.
http://www.jpp.krakow.pl/journal/archive/04_12/pdf/109_04_12_article.pdf
[3] Ikeda, N., Usuda, J., Kato, H., Ishizumi, T., Ichinose, S., Otani, K., Honda, H., Furukawa, K., Okunaka, T. and Tsutsui, H. (2011) New Aspects of Photodynamic Therapy for Central Type Early Stage Lung Cancer. Lasers in Surgery and Medicine, 43, 749-754. http://dx.doi.org/10.1002/lsm.21091
[4] Mimura, S., Narahara, H., Otani, T. and Okuda, S. (1999) Progress of Photodynamic Therapy in Gastric Cancer. Diagnostic and Therapeutic Endoscopy, 5, 175-182. http://dx.doi.org/10.1155/dte.5.175
[5] Tanaka, M., Kinoshita, M., Yoshihara, Y., Shinomiya, N., Seki, S., Nemoto, K., Hirayama, T., Dai, T., Huang, L., Hamblin, M.R. and Morimoto, Y. (2012) Optimal Photosensitizers for Photodynamic Therapy of Infections Should Kill Bacteria but Spare Neutrophils. Photochemistry and Photobiology, 88, 227-232. http://dx.doi.org/10.1111/j.1751-1097.2011.01005.x
[6] Allison, R. R. and Moghissi, K. (2013) Photodynamic Therapy (pdt): Pdt Mechanisms. Clinical Endo- scopy, 46, 24-29. http://dx.doi.org/10.5946/ce.2013.46.1.24
[7] Saini, R. and Poh, C.F. (2013) Photodynamic Therapy: A Review and Its Prospective Role in the Management of Oral Potentially Malignant Disorders. Oral Diseases, 19, 440-451.
http://dx.doi.org/10.1111/odi.12003
[8] Opitz, I., Krueger, T., Pan, Y., Altermatt, H.J., Wagnieres, G. and Ris, H.B. (2006) Preclinical Comparison of Mthpc and Verteporfin for Intracavitary Photodynamic Therapy of Malignant Pleural Mesothelioma. European Surgical Research, 38, 333-339. http://dx.doi.org/10.1159/000094028
[9] Huggett, M.T., Jermyn, M., Gillams, A., Illing, R., Mosse, S., Novelli, M., Kent, E., Bown, S.G., Hasan, T., Pogue, B.W. and Pereira, S.P. (2014) Phase i/ii Study of Verteporfin Photodynamic Therapy in Locally Advanced Pancreatic Cancer. British Journal of Cancer, 110, 1698-1704.
http://dx.doi.org/10.1038/bjc.2014.95
[10] Tanaka, M., Uchibayashi, T., Obata, T. and Sasaki, T. (1995) Photodynamic Therapy of Photofrin ii and Excimer Dye Laser on Experimental Tumors. Cancer Letters, 90, 163-169.
http://dx.doi.org/10.1016/0304-3835(95)03699-W
[11] Magaraggia, M., Marigo, L., Pagnan, A., Jori, G. and Visona, A. (2007) Porphyrin-Photosensitized Processes: Their Applications in the Prevention of Arterial Restenosis. Cardiovascular & Hematological Agents in Medicinal Chemistry, 5, 278-288.
http://dx.doi.org/10.2174/187152507782109908
[12] Van Lier, J.E. and Spikes, J.D. (1989) The Chemistry, Photophysics and Photosensitizing Properties of Phthalocyanines. Ciba Foundation Symposium, 146, 17-26.
[13] Gorman, S.A., Brown, S.B. and Griffiths, J. (2006) An Overview of Synthetic Approaches to Porphyrin, Phthalocyanine, and Phenothiazine Photosensitizers for Photodynamic Therapy. Journal of Environmental Pathology, Toxicology and Oncology, 25, 79-108.
http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.v25.i1-2.50
[14] Yoshiyama, H., Shibata, N., Sato, T., Nakamura, S. and Toru, T. (2008) Synthesis and Properties of Trifluoroethoxy-Coated Binuclear Phthalocyanine. Chemical Communications, 7, 1977-1979.
http://dx.doi.org/10.1039/b800918j
[15] Reddy, M.R., Shibata, N., Kondo, Y., Nakamura, S. and Toru, T. (2006) Design, Synthesis, and Spectroscopic Investigation of Zinc Dodecakis(trifluoroethoxy)phthalocyanines Conjugated with Deoxyribonucleosides. Angewandte Chemie International Edition, 45, 8163-8166.
http://dx.doi.org/10.1002/anie.200603590
[16] Yoshiyama, H., Shibata, N., Sato, T., Nakamura, S. and Toru, T. (2009) Synthesis of Trifluoroethoxy-Coated Binuclear Phthalocyanines with Click Spacers and Investigation of Their Clamshell Behaviour. Organic & Biomolecular Chemistry, 7, 2265-2269. http://dx.doi.org/10.1039/b902905b
[17] Das, B., Tokunaga, E., Tanaka, M., Sasaki, T. and Shibata, N. (2010) Perfluoroisopropyl Zinc Phthalocyanines Conjugated with Deoxyribonucleosides: Synthesis, Photophysical Properties and in Vitro Photodynamic Activities. European Journal of Organic Chemistry, 2010, 2878-2884.
http://dx.doi.org/10.1002/ejoc.201000179
[18] Uchida, H., Sasaki, T., Tanaka, M., Endo, Y., Nitta, K., Nishikawa, K., Chuman, H., Fukuma, H. and Matsumoto, K. (1987) Response to Antitumor Agents of Murine Transplantable Tumors Implanted onto Chorioallantoic Membrane of Chick Embryo. Japanese Journal of Cancer Research, 78, 729-736.
[19] Nishikawa, K., Sasaki, T., Tanaka, M., Uchida, H., Endo, Y., Fukuma, H., Chuman, H., Beppu, Y., Matsumoto, K. and Nitta, K. (1987) Experimental Model for Predicting Metastatic Ability of Tumors Using Chick Embryo. Japanese Journal of Clinical Oncology, 17, 319-325.
[20] Shoin, K., Yamashita, J., Enkaku, F., Sasaki, T., Tanaka, M. and Endo, Y. (1991) Chick Embryo Assay as Chemosensitivity Test for Malignant Glioma. Cancer Science, 82, 1165-1170.
http://dx.doi.org/10.1111/j.1349-7006.1991.tb01772.x
[21] Tanaka, M., Matsuda, A., Terao, T. and Sasaki, T. (1992) Antitumor Activity of a Novel Nucleoside, 2'-C-cyano-2'-deoxy-1-β-D-arabinofuranosylcytosine (CNDAC) against Murine and Human Tumors. Cancer Letters, 64, 67-74. http://dx.doi.org/10.1016/0304-3835(92)90024-P
[22] Yoshida, T., Tokashiki, R., Ito, H., Shimizu, A., Nakamura, K., Hiramatsu, H., Tsukahara, K., Shimizu, S., Takata, D., Okamoto, I. and Suzuki, M. (2008) Therapeutic Effects of a New Photosensitizer for Photodynamic Therapy of Early Head and Neck Cancer in Relation to Tissue Concentration. Auris Nasus Larynx, 35, 545-551. http://dx.doi.org/10.1016/j.anl.2007.10.008
[23] Loftsson, T. and Masson, M. (2001) Cyclodextrins in Topical Drug Formulations: Theory and Practice. International Journal of Pharmaceutics, 225, 15-30.
http://dx.doi.org/10.1016/S0378-5173(01)00761-X
[24] Carrier, R.L., Miller, L.A. and Ahmed, I. (2007) The Utility of Cyclodextrins for Enhancing Oral Bioavailability. Journal of Controlled Release, 123, 78-99.
http://dx.doi.org/10.1016/j.jconrel.2007.07.018
[25] Sharma, K.V., Bowers, N. and Davids, L.M. (2011) Photodynamic Therapy-Induced Killing Is Enhanced in Depigmented Metastatic Melanoma Cells. Cell Biology International, 35, 939-944.
http://dx.doi.org/10.1042/CBI20110103
[26] Calzavara-Pinton, P.G. (1995) Repetitive Photodynamic Therapy with Topical Delta-Aminolevulinic Acid as an Appropriate Approach to the Routine Treatment of Superficial Non-Melanoma Skin Tumours. Journal of Photochemistry and Photobiology B, 29, 53-57.
http://dx.doi.org/10.1016/1011-1344(95)90253-8
[27] Tanaka, M., Tatsuzawa, Y., Uchida, H., Watanabe, Y. and Sasaki, T. (1993) Chemosensitivity Testing of Advanced Lung Cancer by the Chick Embryo Assay. Annals of Cancer Research and Therapy, 2, 217-222. http://dx.doi.org/10.4993/acrt1992.2.217

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