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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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

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Ferrosoferric Oxide
Nanoparticles
Melanoma
Growth
Magnetic Fields
Iron
Cell death
Magnetic fields
Magnetite Nanoparticles
Cell Death
Fever
Bearings (structural)
Melanosomes
Experimental Melanomas
Induced Hyperthermia
Monophenol Monooxygenase
Agaricales

All Science Journal Classification (ASJC) codes

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) Is a nanoparticle for the targeted growth suppression of melanoma cells. / Sato, Makito; Yamashita, Toshiharu; Ohkura, Masae; Osai, Yasue; Sato, Akiko; Takada, Tomoaki; Matsusaka, Hidenobu; Ono, Ichiro; Tamura, Yasuaki; Sato, Noriyuki; Sasaki, Yasushi; Ito, Akira; Honda, Hiroyuki; Wakamatsu, Kazumasa; Ito, Shosuke; Jimbow, Kowichi.

In: Journal of Investigative Dermatology, Vol. 129, No. 9, 01.09.2009, p. 2233-2241.

Research output: Contribution to journalArticle

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, vol. 129, no. 9, pp. 2233-2241. https://doi.org/10.1038/jid.2009.39
Sato, Makito ; Yamashita, Toshiharu ; Ohkura, Masae ; Osai, Yasue ; Sato, Akiko ; Takada, Tomoaki ; Matsusaka, Hidenobu ; Ono, Ichiro ; Tamura, Yasuaki ; Sato, Noriyuki ; Sasaki, Yasushi ; Ito, Akira ; Honda, Hiroyuki ; Wakamatsu, Kazumasa ; Ito, Shosuke ; Jimbow, Kowichi. / N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) Is a nanoparticle for the targeted growth suppression of melanoma cells. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 9. pp. 2233-2241.
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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.",
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AU - Sato, Makito

AU - Yamashita, Toshiharu

AU - Ohkura, Masae

AU - Osai, Yasue

AU - Sato, Akiko

AU - Takada, Tomoaki

AU - Matsusaka, Hidenobu

AU - Ono, Ichiro

AU - Tamura, Yasuaki

AU - Sato, Noriyuki

AU - Sasaki, Yasushi

AU - Ito, Akira

AU - Honda, Hiroyuki

AU - Wakamatsu, Kazumasa

AU - Ito, Shosuke

AU - Jimbow, Kowichi

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N2 - 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.

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