Intracellular hyperthermia for cancer using magnetite cationic liposomes

Shinkai, Masashige; Yanase, Mitsugu; Suzuki, Masataka; Honda, Hiroyuki; Wakabayashi, Toshihiko; Yoshida, Jun; Kobayashi, Takeshi

doi:10.1016/s0304-8853(98)00586-1

Cited by 269 publications

(238 citation statements)

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“…The MCLs were prepared with colloidal magnetite and a lipid mixture consisting of N-(a-trimethylammonioacetyl)-didodecyl-d-glutamate chloride, dilauroylphosphatidyl-choline, and dioleoylphosphatidyl-ethanolamine in a 1:2:2 molar ratio as previously described. 6 All MCL concentrations are expressed as the net magnetite concentration.…”

Section: Preparation Of Mcls and Hyperthermia Treatmentmentioning

confidence: 99%

“…5 We have developed magnetite cationic liposomes (MCLs) for intracellular hyperthermia. 6,7 The hyperthermic effect of MCLs was examined in an in vivo study, and complete tumor regression was observed. 8 Since some researchers have reported that heat treatment itself can enhance the immunogenicity of cancer cells, [9][10][11][12] we previously investigated hyperthermia-induced antitumor immunity in T-9 rat glioma cells in vivo.…”

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confidence: 99%

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Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles

et al. 2003

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Heat shock proteins (HSPs) are recognized as significant participants in immune reactions. We previously reported that expression of HSP70 in response to hyperthermia, produced using our original magnetite cationic liposomes (MCLs), induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by hsp70 gene transfer. A human hsp70 gene mediated by cationic liposomes was injected into a B16 melanoma nodule in C57BL/6 mice in situ. At 24 hours after the injection of the hsp70 gene, MCLs were injected into melanoma nodules in C57BL/6 mice, which were subjected to an alternating magnetic field for 30 minutes. The temperature at the tumor reached 431C and was maintained by controlling the magnetic field intensity. The combined treatment strongly arrested tumor growth over a 30-day period, and complete regression of tumors was observed in 30% (3/10) of mice. Systemic antitumor immunity was induced in the cured mice. This study demonstrates that this novel therapeutic strategy combining the use of hsp70 gene therapy and hyperthermia using MCLs may be applicable to patients with advanced malignancies. Cancer Gene Therapy (2003) 10, 918-925. doi:10.1038/sj.cgt.7700648Keywords: heat shock proteins; hyperthermia; magnetite; cancer immunotherapy H yperthermia is a promising approach for cancer therapy. 1,2 However, the inevitable technical problem with hyperthermia is the difficulty in heating only the local tumor region to the intended temperature without damaging the surrounding normal tissue. Magnetic nanoparticles have been used for hyperthermia treatment in an attempt to overcome these disadvantages. 3,4 Magnetic nanoparticles generate heat in an alternating magnetic field (AMF) due to hysteresis loss. 5 We have developed magnetite cationic liposomes (MCLs) for intracellular hyperthermia. 6,7 The hyperthermic effect of MCLs was examined in an in vivo study, and complete tumor regression was observed. 8 Since some researchers have reported that heat treatment itself can enhance the immunogenicity of cancer cells, 9-12 we previously investigated hyperthermia-induced antitumor immunity in T-9 rat glioma cells in vivo. 13 This induced immunity continued for an extended period of time, and the rats treated with hyperthermia completely rejected T-9 cells as a metastasis model. Moreover, we investigated the mechanisms of antitumor immunity induced by intracellular hyperthermia with regard to the role of heat shock proteins (HSPs). 14,15 HSPs are a highly conserved group of intracellular proteins whose synthesis is increased by a large variety of stressors including heat shock. 16 As expression of HSP70 protects cells from heat-induced apoptosis, 17 HSP70 expression is considered a complicating factor in hyperthermia. On the other hand, recent reports have shown the importance of HSPs, such as HSP70, HSP90, and glucose-regulated protein 96 (gp96), in immune reactions. 18,19 A possible mechanism by which HSPs influence tumor cell immunogenicity is associated with...

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Section: Preparation Of Mcls and Hyperthermia Treatmentmentioning

confidence: 99%

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Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles

et al. 2003

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“…After incubation for 1, 4 or 8 h, the cells were washed with 1 ml PBS twice and harvested by a rubber policeman. The quantity of adsorbed magnetite was measured by our previous method (Shinkai et al, 1996).…”

Section: Fmls Uptake By Tumor Cells In Vitromentioning

confidence: 99%

“…We have developed "magnetite cationic liposomes (MCLs)" as a "magnetoliposomes (MLs)" containing cationic lipid (Shinkai et al, 1996). MCLs show ten times higher affinity for glioma cells than that of the MLs with neutral charge, because of the positive charge on the surface.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Tumor-Specific Magnetoliposomes and Their Application for Hyperthermia.

Shinkai

Kitade

et al. 2001

J. Chem. Eng. Japan / JCEJ

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Magnetoliposomes (MLs) were conjugated with an antibody fragment to give specificity to a tumor. The antibody fragment was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The immobilization of the antibody fragment was optimal when the content of EMC-DPPE was 10-wt% and the reaction time for immobilization was 18 h. The Fab′ fragment-conjugating MLs (FMLs) were 2.4 times higher molar immobilization density compared with the method using the whole antibody. The targetability of the FMLs to the glioma cells, U251-SP, was then investigated. The amount of FMLs uptake reached 85 pg/cell in an in vitro experiment using plastic dishes. In an in vivo experiment using glioma-harboring mice, 260 µg of the FMLs per 1 g of tumor tissue accumulated (tumor sizes was 0.1 cm 3 ), which corresponded to approximately 60% of the total injection. This value was 7 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using the alternating magnetic field irradiation. The temperature of tumor tissue increased to 43°C and the growth of the tumor was found to be arrested over 2 weeks. These results indicate the FMLs could target the glioma cells in vitro and in vivo, and are efficiently applicable to the hyperthermia of tumor.

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“…5 We subsequently developed magnetite cationic liposomes (MCLs) for use as an intracellular heating mediator. 6 MCLs were developed to show improved adsorption and accumulation in tumor cells and have a 10-fold higher affinity for tumor cells than for neutrally charged magnetoliposomes due to electrostatic interaction with the negatively-charged cell membrane. 7 The hyperthermic effects of MCLs were examined in an in vivo study, and complete tumor regression was observed.…”

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Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles

Tanaka

Ito

Kobayashi

et al. 2005

Intl Journal of Cancer

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Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in regulating immune responses in cancer and have recently been shown to be activated by heat shock proteins (HSPs). We previously reported that HSP70 expression after hyperthermia induces antitumor immunity. Our hyperthermia system using magnetite cationic liposomes (MCLs) induced necrotic cell death that was correlated with HSP70 release. In the present study, we investigated the therapeutic effects of DC therapy combined with MCL-induced hyperthermia on mouse melanoma. In an in vitro study, when immature DCs were pulsed with mouse B16 melanoma cells heated at 43°C, major histocompatibility complex (MHC) class I/II, costimulatory molecules CD80/ CD86 and CCR7 in the DCs were upregulated, thus resulting in DC maturation. C57BL/6 mice bearing a melanoma nodule were subjected to combination therapy using hyperthermia and DC immunotherapy in vivo by means of tumor-specific hyperthermia using MCLs and directly injected immature DCs. Mice were divided into 4 groups: group I (control), group II (hyperthermia), group III (DC therapy) and group IV (hyperthermia 1 DC therapy). Complete regression of tumors was observed in 60% of mice in group IV, while no tumor regression was seen among mice in the other groups. Increased cytotoxic T lymphocyte (CTL) and natural killer (NK) activity was observed on in vitro cytotoxicity assay using splenocytes in the cured mice treated with combination therapy, and the cured mice rejected a second challenge of B16 melanoma cells. This study has important implications for the application of MCL-induced hyperthermia plus DC therapy in patients with advanced malignancies as a novel cancer therapy. ' 2005 Wiley-Liss, Inc.Key words: hyperthermia; dendritic cell; antitumor immunity; magnetite cationic liposome; melanoma Hyperthermia has been used for many years to treat a wide variety of tumors in both experimental animals and patients. 1 The most commonly used heating method in clinical settings is capacitive heating using a radiofrequency (RF) electric field. 2 However, the problem with capacitive heating using an RF electric field is the difficulty in heating only the local tumor region at the intended temperature without damaging normal tissue, because electromagnetic energy is conducted from outside the body by penetrating normal tissue and is imperfectly transduced to heat; the heating characteristics are influenced by various factors, such as tumor size, position of electrodes, and adhesion of electrodes at uneven sites. Magnetic nanoparticles have thus been applied to hyperthermia in an attempt to overcome these disadvantages. 3,4 Magnetic nanoparticles act as a transducer to change electromagnetic energy to heat; such nanoparticles generate heat in an alternating magnetic field (AMF) due to hysteresis loss. As a result, only tissue accumulating magnetite nanoparticles is heated. 5 We subsequently developed magnetite cationic liposomes (MCLs) for use as an intracellular heating mediator. 6 MCLs were dev...

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Intracellular hyperthermia for cancer using magnetite cationic liposomes

Cited by 269 publications

References 13 publications

Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles

Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles

Preparation of Tumor-Specific Magnetoliposomes and Their Application for Hyperthermia.

Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles

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