Complete Regression of Hereditary Melanoma in a Mouse Model by Repeated Hyperthermia Using Magnetite Cationic Liposomes

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  • ITO AKIRA
    Department of Biotechnology, School of Engineering, Nagoya University
  • NAKAHARA YOKO
    Department of Biotechnology, School of Engineering, Nagoya University
  • FUJIOKA MASATAKE
    Department of Biotechnology, School of Engineering, Nagoya University
  • KOBAYASHI TAKESHI
    Department of Biotechnology, School of Engineering, Nagoya University School of Bioscience and Biotechnology, Chubu University
  • TAKEDA KOZUE
    Department of Immunology, Nagoya University Graduate School of Medicine
  • NAKASHIMA IZUMI
    Department of Immunology, Nagoya University Graduate School of Medicine
  • HONDA HIROYUKI
    Department of Biotechnology, School of Engineering, Nagoya University Corresponding author

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  • 正電荷リポソーム包埋型マグネタイトを用いた繰り返しハイパーサーミアによるマウス遺伝性メラノーマの完全退縮

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Abstract

Magnetite cationic liposomes (MCLs) have a positive surface charge, and have been used as heating mediators for intracellular hyperthermia because they generate heat in an alternating magnetic field (AMF) due to hysteresis loss. In our previous paper, hyperthermia using MCLs was applied to animals having several types of tumor, and a strong antitumor effect was observed in those animal models using transplantable tumor cell lines. In the present study, our protocol was applied to a hereditary melanoma model ; primary skin melanoma developing in a metallothionein (MT) -I/ret transgenic mouse line. MCLs were injected into a melanoma nodule (size, 5-7 mm) in MT/ret transgenic mice, which were subjected to AMF for 30 min. The temperature at the surface of the tumor reached 45°C and was maintained by adjusting the magnetic field intensity. Hyperthermia treatment was repeated three times at 24 h intervals (repeated hyperthermia ; RH), and RH was carried out until complete tumor regression was observed. Complete tumor regression was achieved in all mice treated once, twice or three times with RH. Furthermore, tumors successfully treated by RII did not undergo regrowth for 120 d post-treatment, and significant elongation of survival was observed. These results suggest that MCL-mediated hyperthermia is a potent approach to treat malignant melanoma.

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