Open AccessSimultaneous hyperthermia‐chemotherapy effect by arterial injection of Fe(Salen) for femur tumor
Author(s) -
Umemura Masanari,
Islam Md. Rafikul,
Fukumura Hidenobu,
Sato Itaru,
Kawabata Yusuke,
Matsuo Kousuke,
Nakakaji Rina,
Nagasako Akane,
Ohtake Makoto,
Takayuki Fujita,
Yokoyama Utako,
Nakayama Tomohiro,
Eguchi Haruki,
Ishikawa Yoshihiro
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13851
Subject(s) - hyperthermia , ethylenediamine , chemistry , magnetic hyperthermia , materials science , magnetic nanoparticles , medicine , nanoparticle , nanotechnology , organic chemistry
We previously identified a novel nanomagnetic particle, N , N ′ ‐ bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet‐guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra‐arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra‐arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra‐arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra‐arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia‐chemotherapy in the future.