N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) Is a nanoparticle for the targeted growth suppression of melanoma cells

Makito Sato, Toshiharu Yamashita, Masae Ohkura, Yasue Osai, Akiko Sato, Tomoaki Takada, Hidenobu Matsusaka, Ichiro Ono, Yasuaki Tamura, Noriyuki Sato, Yasushi Sasaki, Akira Ito, Hiroyuki Honda, Kazumasa Wakamatsu, Shosuke Ito, Kowichi Jimbow

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25 Citations (Scopus)

Abstract

A magnetite nanoparticle, NPrCAP/M, was produced for intracellular hyperthermia treatment of melanoma by conjugating N-propionyl-cysteaminylphenol (NPrCAP) with magnetite and used for the study of selective targeting and degradation of melanoma cells. NPrCAP/M, like NPrCAP, was integrated as a substrate in the oxidative reaction by mushroom tyrosinase. Melanoma, but not non-melanoma, cells incorporated larger amounts of iron than magnetite from NPrCAP/M. When mice bearing a B16F1 melanoma and a lymphoma on opposite flanks were given NPrCAP/M, iron was observed only in B16F1 melanoma cells and iron particles (NPrCAP/M) were identified within late-stage melanosomes by electron microscopy. When cells were treated with NPrCAP/M or magnetite and heated to 43°C by an external alternating magnetic field (AMF), melanoma cells were degraded 1.7-to 5.4-fold more significantly by NPrCAP/M than by magnetite. Growth of transplanted B16 melanoma was suppressed effectively by NPrCAP/M-mediated hyperthermia, suggesting a clinical application of NPrCAP/M to lesional therapy for melanoma. Finally, melanoma cells treated with NPrCAP/M plus AMF showed little sub-G1 fraction and no caspase 3 activation, suggesting that the NPrCAP/M-mediated hyperthermia induced non-apoptotic cell death. These results suggest that NPrCAP/M may be useful in targeted therapy for melanoma by inducing non-apoptotic cell death after appropriate heating by the AMF.

Original languageEnglish
Pages (from-to)2233-2241
Number of pages9
JournalJournal of Investigative Dermatology
Volume129
Issue number9
DOIs
Publication statusPublished - Sep 1 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Sato, M., Yamashita, T., Ohkura, M., Osai, Y., Sato, A., Takada, T., Matsusaka, H., Ono, I., Tamura, Y., Sato, N., Sasaki, Y., Ito, A., Honda, H., Wakamatsu, K., Ito, S., & Jimbow, K. (2009). N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) Is a nanoparticle for the targeted growth suppression of melanoma cells. Journal of Investigative Dermatology, 129(9), 2233-2241. https://doi.org/10.1038/jid.2009.39