title: A magnetic anti-cancer compound for magnet-guided delivery and magnetic resonance imaging.
abstract: Research on controlled drug delivery for cancer chemotherapy has focused mainly on ways to deliver existing anti-cancer drug compounds to specified targets, e.g., by conjugating them with magnetic particles or encapsulating them in micelles. Here, we show that an iron-salen, i.e., μ-oxo N,N'- bis(salicylidene)ethylenediamine iron (Fe(Salen)), but not other metal salen derivatives, intrinsically exhibits both magnetic character and anti-cancer activity. X-Ray crystallographic analysis and first principles calculations based on the measured structure support this. It promoted apoptosis of various cancer cell lines, likely, via production of reactive oxygen species. In mouse leg tumor and tail melanoma models, Fe(Salen) delivery with magnet caused a robust decrease in tumor size, and the accumulation of Fe(Salen) was visualized by magnetic resonance imaging. Fe(Salen) is an anti-cancer compound with magnetic property, which is suitable for drug delivery and imaging. We believe such magnetic anti-cancer drugs have the potential to greatly advance cancer chemotherapy for new theranostics and drug-delivery strategies.
authors.affiliation: 1] Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, Japan [2] Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Biochemical Engineering, Faculty of Engineering, Yamagata University, Yonezawa, Yamagata, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kurotani
authors.affiliation: Department of orthopedics, Machida Hospital, Machida, Tokyo.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Fukumura
authors.affiliation: Department of Oral Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Sato
authors.affiliation: 1] Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, Japan [2] Nanoparticles by Design Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Japan.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Electrical Engineering, Graduate School of Engineering, Kyoto University, Kyoto, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Amemiya
authors.affiliation: Department of Physiology, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Sato
authors.affiliation: RIKEN, Research Infrastructure Group, SR Life Science Instrumentation Unit, Hyogo, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Materials Science and Technology Division, Oak Ridge National Laboratory, TN, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Singh
authors.affiliation: Tokyo Neutron Science Laboratory, Institute for Solid State Physics, the University of Tokyo, Shirakata, Tokai, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Chemistry of Functional Molecules, Faculty of Science and Engineering, Konan University, Kobe, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Yokohama City University, Graduate School, Yokohama, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Urano
authors.affiliation: Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: WPI-AIMR &Department of Physics, Graduate School of Science, Tohoku University, Sendai, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Tanigaki
authors.affiliation: RIKEN, Research Infrastructure Group, SR Life Science Instrumentation Unit, Hyogo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D005029:Ethylenediamines; D058185:Magnetite Nanoparticles; C011452:disalicylaldehyde ethylenediamine; D007501:Iron