Treatment of oral cancer using magnetized paclitaxel

Rina Nakakaji; Masanari Umemura; Kenji Mitsudo; Jeong-Hwan Kim; Yujiro Hoshino; Itaru Sato; Takatsugu Masuda; Masahiro Yamamoto; Mitomu Kioi; Toshiyuki Koizumi; Takayuki Fujita; Utako Yokoyama; Masaki Iida; Motohiko Sato; Hiroshi Sato; Shoko Murofushi; Sayaka Shibata; Ichio Aoki; Haruki Eguchi; Iwai Tohnai; Yoshihiro Ishikawa

doi:10.18632/oncotarget.24570

Treatment of oral cancer using magnetized paclitaxel

Oncotarget. 2018 Feb 26;9(21):15591-15605. doi: 10.18632/oncotarget.24570. eCollection 2018 Mar 20.

Authors

Rina Nakakaji^{1

2}, Masanari Umemura¹, Kenji Mitsudo², Jeong-Hwan Kim¹, Yujiro Hoshino³, Itaru Sato^{1

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, Yoshihiro Ishikawa¹

Affiliations

¹ Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
² Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
³ Department of Environment and Natural Sciences, Yokohama National University Graduate School of Environment and Information Sciences, Yokohama, Japan.
⁴ Tokyo Neutron Science Laboratory, Tokyo University Institute for Solid State Physics, Kashiwa, Japan.
⁵ Department of Chemistry of Functional Molecules, Konan University Faculty of Science and Engineering, Kobe, Japan.
⁶ Department of Physiology, Aichi Medical University, Nagakute, Japan.
⁷ Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, Japan.
⁸ Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.

Abstract

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.

Keywords: iron-salen; magnetism; oral cancer; paclitaxel; taxol.