Magnetic Nanoparticle-Mediated Hyperthermia and Induction of Anti-Tumor Immune Responses
Magnetic nanoparticle-mediated hyperthermia (MNHT) can heat tumor tissue to the desired temperature without damaging surrounding normal tissue. The MNHT system consists of targeting tumor with functional magnetic nanoparticles (MNPs) and then applying an
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Magnetic Nanoparticle-Mediated Hyperthermia and Induction of Anti-Tumor Immune Responses Takeshi Kobayashi, Akira Ito, and Hiroyuki Honda
Abstract Magnetic nanoparticle-mediated hyperthermia (MNHT) can heat tumor tissue to the desired temperature without damaging surrounding normal tissue. The MNHT system consists of targeting tumor with functional magnetic nanoparticles (MNPs) and then applying an external alternating magnetic field (AMF) to generate heat in the MNPs. Temperature in the tumor tissue is increased to above 43 C, which causes necrosis of cancer cells but does not damage surrounding normal tissue. Among available MNPs, magnetite has been extensively studied. Recent years have seen remarkable advances in MNHT; both functional MNPs and AMF generators have been developed. By applying MNHT, heat shock proteins (HSPs) are highly expressed within and around tumor tissue, which causes intriguing biological responses such as tumor-specific immune response. These results suggest that MNHT is able to kill not only tumors exposed to heat treatment, but also unheated metastatic tumors at distant sites. Currently, some researchers have started clinical trials, suggesting that the time has come for clinical applications. Keywords Hyperthermia • Magnetic nanoparticles • Magnetic field • Immune responses
T. Kobayashi (*) School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, 487-8501 Kasugai, Aichi, Japan e-mail: [email protected] A. Ito Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan H. Honda Department of Biotechnology, School of Engineering, Nagoya University, Aichi, Nagoya, Japan © Springer Science+Business Media Singapore 2016 S. Kokura et al. (eds.), Hyperthermic Oncology from Bench to Bedside, DOI 10.1007/978-981-10-0719-4_13
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Introduction
Hyperthermia is a promising approach to cancer therapy, in part, because hyperthermia is a physical treatment and can result in fewer side effects than chemotherapy or radiotherapy [1, 2]. A major technical problem with the currently available hyperthermia is the difficulty of heating a local tumor region without damaging normal tissue. A consensus landmark is the threshold temperature of 42.5 C [3], because heat cytotoxicity is markedly higher than 42.5 C. Although such high temperatures can kill a great number of tumor cells, normal tissues are also damaged, especially under the conventional hyperthermia treatments. Therefore, the development of a novel hyperthermia system which can specifically target tumor tissue and heat the tumor above 42.5 C has been highly desired. MNHT is a largely experimental modality for hyperthermia which may overcome these shortcomings [4–7]. The MNHT system consists of targeting functional MNPs to the tumor, and then applying an external AMF to generate heat in the MNPs by mechanisms called as hysteresis loss and Ne´el relaxational loss. Recently, remarkable advances have been seen in MNHT using both tumor-targeted MNPs
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