Dr. Masanari Umemura
Senior lecturer, Cardiovascular Research Institute (CVRI), Yokohama City University Graduate School of Medicine, Yokohama, Japan
Abstract
We previously found a novel magnetic organic compound, N,N’-bis(salicylidene)ethylenediamine iron [Fe(Salen)], as an anticancer agent with the intrinsic magnetic property. In addition to the anticancer effect, Fe(Salen) exhibits the following unique functions: 1) Fe(Salen) can be attracted by a permanent magnet. 2) Fe(Salen) per se generates heat when exposed to an alternating magnetic field (AMF) like the principle of the induction cooker. 3) Fe(Salen) can be visualized by magnetic resonance imaging (MRI).
We identified the chemical key structure of Fe(Salen) to find out the causes of its magnetic property by crystal structure analysis. The result showed that a unique angle configuration of Fe-O-Fe (146.359 °) in the crystal structure of Fe(Salen) plays an important role in generating the original magnetism of Fe(Salen). This angle is well known as the Goodenough-Kanamori rule, which is a classical physics theory. Therefore, we hypothesized that the Fe(Salen) molecule can add an intrinsic magnetic property to the commercially available anticancer drugs by chemically tethering the drug counterpart. Initially, we targeted paclitaxel (PTX) for magnetization with Fe(Salen) because PTX is one of the most studied chemotherapeutic molecules in the history of medicinal chemistry. Finally, we succeeded in covalently linked Fe(Salen) to paclitaxel (PTX) in order to add intrinsic magnetic property. Thus, we called this novel compound magnetized PTX (M-PTX). Because M-PTX has not only the original characteristics of commercially available PTX but also the magnetic property, M-PTX could be applied to magnet-guided drug delivery (DDS) by a magnet and MRI visualization. Moreover, in a mouse oral cancer model, the accumulation of M-PTX by a permanent magnet placed on the tumor resulted in an increasing anticancer effect of M-PTX. Indeed, the permanent magnet significantly increased the anticancer effect of M-PTX compared to that without the magnet or that of control.
Therefore, this innovative covalent coupling technique with Fe(Salen) can improve the therapeutic potency of commercially available drugs. Our aim is to develop novel magnetic compounds to apply for DDS with a permanent magnet and monitor effective drug concentration at the target site by MRI visualization.
Biography
Dr. Masanari Umemura is a senior lecturer, Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan. He obtained his Ph.D. degree from Yokohama City University in 2006. He was a Post-Doctoral fellow in the Rutgers University (University of Medical and Dentistry of New Jersey) from 2010 to 2012. He joined Professor Yoshihiro Ishikawa’s laboratory at Yokohama City University as an assistant professor. Currently Dr. Umemura and colleagues found a novel organic compound with cytotoxic property and intrinsic magnetic property, i.e. Fe(Salen). They reported some novel methods to treat cancers using Fe(Salen). He is developing innovative technology for synthesizing commercially available drugs with intrinsic magnetic property.