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543
梅 村 将 就，他
Abstract
DEVELOPMENT OF TECHNOLOGY FOR NOVEL COMMERCIALLY AVAILABLE COMPOUNDS
WITH INTRINSIC MAGNETIC PROPERTIES
Masanari Umemura 1 ）, Rina Nkakaji
Md Rafikul Islam
, Akane Nagasako 1 ）,
1, 2）
1）
, Makoto Ohtake 3 ）, Kagemichi Ngao 1 , 3 ）,
4）
Hiroko Nemoto , Yuto Mizuno 1 ）, Soichiro Ishikawa 1 , 2 ）,
Fumina Suzuki 1 ）, Yoshihiro Ishikawa 1 ）
Department of Cardiovascular Research Institute (CVRI), Yokohama City University Graduate School of Medicine
Department of Dentistry/Oral and Maxillofacial Surgery/
Orthodontics, Yokohama City University Graduate School of Medicine
Department of Neurosurgery, Yokohama City University Graduate School of Medicine
Department of Surgery, Yokohama City University Graduate School of Medicine
We previously identified a novel magnetic organic compound, N,N'-bis(salicylidene)ethylenediamine iron
[Fe(Salen)], as an anti-cancer agent with intrinsic magnetism. In addition to the anticancer effect, Fe(Salen) exhibited
the following unique characteristics. 1) It can be attracted by a permanent magnet. 2) It per se generates cytotoxic
heat when exposed to an alternating magnetic field (AMF), similar to the principle of an induction cooker. 3) It can
be visualized by magnetic resonance imaging (MRI). Indeed, Fe(Salen) exhibited an anti-cancer effect in various
cancer cell lines.
We found the magnetic chemical key structure of Fe(Salen) generating the magnetic property using Super Photon
ring-8 GeV (Spring 8) (RIKEN) crystal structure analysis. This result showed that the unique angle configuration of
Fe-O-Fe (146.359°) in the crystal structure of Fe(Salen) plays an important role in generating magnetism. This angle
is well known as the Goodenough-Kanamori rule. Based on the proven magnetic performance of Fe(Salen) that is
attributed to its specific molecular structure, we hypothesized that the Fe(Salen) molecule can endow a commercially
available anti-cancer drug, paclitaxel (PTX), with an intrinsic magnetic property by chemically tethering the drug
counterpart. PTX is one of the most studied chemotherapeutic molecules in the history of medicinal chemistry. In
this study, we covalently linked Fe(Salen) to PTX to obtain a magnetized PTX conjugate (M-PTX), which exhibited
magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX exhibited its anti-cancer
effect in various cancer cell lines. In a mouse oral cancer model, a permanent magnet placed on the body surface
adjacent to the tumor showed an accumulation of M-PTX. Moreover, the magnet greatly increased the anti-cancer
effect of M-PTX. Therefore, such a covalent coupling technique can be an effective method for improving the
therapeutic index of clinically used agents. Our aim is to develop novel magnetic compounds and to apply them in a
drug delivery system with a permanent magnet or alternating magnetic fields.
544
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