Treatment of oral cancer using magnetized paclitaxel
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Rina Nakakaji1,2,*, Masanari Umemura1,*, Kenji Mitsudo2, Jeong-Hwan Kim1, Yujiro Hoshino3, Itaru Sato1,2, Takatsugu Masuda4, Masahiro Yamamoto5, Mitomu Kioi2, Toshiyuki Koizumi2, Takayuki Fujita1, Utako Yokoyama1, Masaki Iida2, Motohiko Sato6, Hiroshi Sato7, Shoko Murofushi7, Sayaka Shibata8, Ichio Aoki8, Haruki Eguchi7, Iwai Tohnai2 and Yoshihiro Ishikawa1
1Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan
2Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
3Department of Environment and Natural Sciences, Yokohama National University Graduate School of Environment and Information Sciences, Yokohama, Japan
4Tokyo Neutron Science Laboratory, Tokyo University Institute for Solid State Physics, Kashiwa, Japan
5Department of Chemistry of Functional Molecules, Konan University Faculty of Science and Engineering, Kobe, Japan
6Department of Physiology, Aichi Medical University, Nagakute, Japan
7Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, Japan
8Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan
*These authors contributed equally to this work
Masanari Umemura, email: [email protected]
Yoshihiro Ishikawa, email: [email protected]
Keywords: iron-salen; taxol; oral cancer; paclitaxel; magnetism
Received: July 14, 2017 Accepted: February 20, 2018 Epub: February 26, 2018 Published: March 20, 2018
N,N’-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/quantitation of drug distribution.
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