A magnetic anti-cancer compound for magnet-guided delivery and magnetic resonance imaging.

Seiichi Inoue,Masanari Umemura,Naoyuki Amemiya,Ichio Aoki,Jin Liu ,Jeong Hwan Kim ,Reiko Kurotani,Yoshihiro Ishikawa,Masaki Yamamoto,David J Singh,Kunio Hirata,Hisashi Eguchi ,Tsutomu Urano,Takatsugu Masuda,Yujiro Hoshino,Masahiro Yamamoto,Keiichiro Yoshida,Mamoru Sato,Katsumi Tanigaki,Itaru Sato,Hidenobu Fukumura,Motohiko Sato

doi:10.1038/srep09194

Abstract

Research on controlled drug delivery for cancer chemotherapy has focused mainly on ways to deliver existing anti-cancer drug compounds to specified targets, e.g., by conjugating them with magnetic particles or encapsulating them in micelles. Here, we show that an iron-salen, i.e., μ-oxo N,N'- bis(salicylidene)ethylenediamine iron (Fe(Salen)), but not other metal salen derivatives, intrinsically exhibits both magnetic character and anti-cancer activity. X-Ray crystallographic analysis and first principles calculations based on the measured structure support this. It promoted apoptosis of various cancer cell lines, likely, via production of reactive oxygen species. In mouse leg tumor and tail melanoma models, Fe(Salen) delivery with magnet caused a robust decrease in tumor size, and the accumulation of Fe(Salen) was visualized by magnetic resonance imaging. Fe(Salen) is an anti-cancer compound with magnetic property, which is suitable for drug delivery and imaging. We believe such magnetic anti-cancer drugs have the potential to greatly advance cancer chemotherapy for new theranostics and drug-delivery strategies.

Highlights

Research on controlled drug delivery for cancer chemotherapy has focused mainly on ways to deliver existing anti-cancer drug compounds to specified targets, e.g., by conjugating them with magnetic particles or encapsulating them in micelles
We describe a previously un-investigated salen iron derivative, i.e., m-oxo N,N9- bis(salicylidene)ethylenediamine iron (Fe(Salen)), that shows both cytotoxicity and magnetization. We demonstrate that such properties can be used, in an animal cancer model, for magnet-guided drug delivery and visualization of the accumulated drug by magnetic resonance (MR) imaging
As reported previously[11,12], we confirmed that some metal salen derivatives, such as N,N9-bis(salicylidene) ethylenediamine chromium (Cr-salen) but not N,N9-bis(salicylidene) ethylenediamine manganese (Mn-salen), exhibited potent anti-cancer properties alike cisplatin (Fig. 1a, b and c)

Summary

Introduction

Research on controlled drug delivery for cancer chemotherapy has focused mainly on ways to deliver existing anti-cancer drug compounds to specified targets, e.g., by conjugating them with magnetic particles or encapsulating them in micelles. Superparamagnetic particles have been combined with drugs[3,4] via ionic conjugation or by emulsification in micelles[5] Their usefulness has been proposed for a broad range of biological applications, including cancer chemotherapy, tissue repair, hyperthermic therapy, or magnetic resonance (MR) imaging contrast enhancement[6]. We describe a previously un-investigated salen iron derivative, i.e., m-oxo N,N9- bis(salicylidene)ethylenediamine iron (Fe(Salen)), that shows both cytotoxicity and magnetization We demonstrate that such properties can be used, in an animal cancer model, for magnet-guided drug delivery and visualization of the accumulated drug by MR imaging

Methods

Results

Conclusion