title: Hyperthermia and chemotherapy using Fe(Salen) nanoparticles might impact glioblastoma treatment.
abstract: We previously reported that μ-oxo N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)], a magnetic organic compound, has direct anti-tumor activity, and generates heat in an alternating magnetic field (AMF). We showed that Fe(Salen) nanoparticles are useful for combined hyperthermia-chemotherapy of tongue cancer. Here, we have examined the effect of Fe(Salen) on human glioblastoma (GB). Fe(Salen) showed in vitro anti-tumor activity towards several human GB cell lines. It inhibited cell proliferation, and its apoptosis-inducing activity was greater than that of clinically used drugs. Fe(Salen) also showed in vivo anti-tumor activity in the mouse brain. We evaluated the drug distribution and systemic side effects of intracerebrally injected Fe(Salen) nanoparticles in rats. Further, to examine whether hyperthermia, which was induced by exposing Fe(Salen) nanoparticles to AMF, enhanced the intrinsic anti-tumor effect of Fe(Salen), we used a mouse model grafted with U251 cells on the left leg. Fe(Salen), BCNU, or normal saline was injected into the tumor in the presence or absence of AMF exposure. The combination of Fe(Salen) injection and AMF exposure showed a greater anti-tumor effect than did either Fe(Salen) or BCNU alone. Our results indicate that hyperthermia and chemotherapy with single-drug nanoparticles could be done for GB treatment.
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.|Department of Neurosurgery, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohtake
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.|Department of Oral and Maxillofacial Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Sato
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.|Department of Neurosurgery, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Oda
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Nagasako
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Utako
authors.initials: U
authors.lastname: Yokoyama
authors.affiliation: Department of Veterinary Medicine, Nihon University, Fujisawa, 252-8510, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, 240-8501, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, 235-0031, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ishiba
authors.affiliation: Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, 235-0031, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tokura
authors.affiliation: Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, 235-0031, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hara
authors.affiliation: Heat and Fluid Dynamics Department, Research Laboratory, IHI Corporation, Yokohama, 235-0031, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Muramoto
authors.affiliation: Collage of Science and Engineering, Kanazawa University, Kakuma, 920-1192, Japan.
authors.forename: Sotoshi
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Neutron Science Laboratory, Institute for Solid State Physics, the University of Tokyo, Shirakata, Tokai, 319-1106, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, 263-8555, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Electrical and Computer Engineering, Yokohama National University, Yokohama, 240-8501, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takemura
authors.affiliation: Department of Neurosurgery, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Murata
authors.affiliation: Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, 235-0031, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Neurosurgery, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kawahara
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005029:Ethylenediamines / Q000008:administration & dosage* / Q000494:pharmacology; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D051379:Mice; D053758:Nanoparticles; D051381:Rats; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005029:Ethylenediamines; C011452:disalicylaldehyde ethylenediamine