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Journal of Skin Cancer
Volume 2013, Article ID 742925, 12 pages
Review Article

Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles

1Institute of Dermatology & Cutaneous Sciences, 1-27 Odori West 17, Chuo-ku, Sapporo 060-0042, Japan
2Department of Dermatology, School of Medicine, Sapporo Medical University, South 1 West 16, Chuo-ku, Sapporo 060-8556, Japan
3Department of Chemistry, School of Health Sciences, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
4Department of Pathology 1, School of Medicine, Sapporo Medical University, South 1 West 16, Chuo-ku, Sapporo 060-8556, Japan
5Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
6Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
7Meito Sangyo Co., Ltd., 25-5 Kaechi, Nishibiwajima-cho, Kiyosu, Aichi 452-0067, Japan
8Faculty of Health and Welfare, Kawasaki University of Medical Welfare, 288 Matsushimai, Kurashiki, Okayama 701-0193, Japan
9Department of Hyperthermia Medical Research Laboratory, Louis Pasteur Center for Medical Research, 103-5, Tanakamonzen-cho, Sakyo-ku, Kyoto 606-8225, Japan
10Yamamoto Vinita Co., Ltd., 3-12 ueshio 6, Tennoji-ku, Osaka 543-0002, Japan
11Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan

Received 9 August 2012; Revised 8 January 2013; Accepted 22 January 2013

Academic Editor: Mohammed Kashani-Sabet

Copyright © 2013 Kowichi Jimbow et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system.