JCT  Vol.6 No.1 , January 2015
Photodynamic Therapy Using Novel Zinc Phthalocyanine Derivatives and a Diode Laser for Superficial Tumors in Experimental Animals
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.

Cite this paper
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.
[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.

[2]   Baldea, I. and Filip, A.G. (2012) Photodynamic Therapy in Melanoma—An Update. Journal of Physiology and Pharmacology, 63, 109-118.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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