Simultaneous hyperthermia-chemotherapy effect by arterial injection of Fe(Salen) for femur tumor.

Abstract

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.

• Authors: Masanari Umemura, Md Rafikul Islam, Hidenobu Fukumura, Itaru Sato, Yusuke Kawabata, Kousuke Matsuo, Rina Nakakaji, Akane Nagasako, Makoto Ohtake, Fujita Takayuki, Utako Yokoyama, Tomohiro Nakayama, Haruki Eguchi, Yoshihiro Ishikawa
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 1 Pg. 356-365 (Jan 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 30375142 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Iron Compounds
• mu-oxo N,N'- bis(salicylidene)ethylenediamine iron
• Methotrexate

Topics

• Animals
• Carcinoma, Squamous Cell (therapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Delivery Systems (methods)
• Femoral Neoplasms (therapy)
• Humans
• Hyperthermia, Induced (methods)
• Injections, Intra-Arterial
• Injections, Intravenous
• Iron Compounds (administration & dosage, pharmacology)
• Magnetic Fields
• Male
• Methotrexate (administration & dosage, pharmacology)
• Nanoparticles (administration & dosage)
• Rabbits
• Rats, Sprague-Dawley
• Xenograft Model Antitumor Assays