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

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.

Magnetic metal-complex-conducting copolymer core–shell nanoassemblies for a single-drug anticancer platform

“…When Fe(salen) was dispersed in aqueous solution (saline), it immediately aggregated due to its hydrophobic nature, exhibiting ferromagnetic-like behavior by the attachment of a magnet, in accordance with our previous reports. 13,14 Prolonged exposure to air (47 days) during the recrystallization process caused a significant loss of magnetism of Fe(salen) NPs, presumably due to oxidation. On the other hand, the CSNAs showed stable magnetism for at least 6 months of subsequent air exposure, implying that the formation of the homogeneous PPy-shell prevents oxidative modification of the Fe(salen) core.…”

“…The recrystallized Fe(salen) has a triclinic crystal structure (α, β and γ ≠ 90°) due to Fe(salen) dimer formation, as reported earlier. 13 Figure S1b). No other elements were detected.…”

“…5,6 To address these problems, a single low-molecular-weight drug component having multifunctional capabilities is required. Metal complexes are useful for this purpose [13][14][15][16] because a metal complex is not only small but also can be therapeutically active with magnetic 13,14 or optical properties. 15,16 Therefore, a single-step fabrication method for a metal-salt-free, magnetic metal-complex-based local DDS platform might shift the synthetic paradigm to realize advanced DDS applications.…”

“…We have previously reported a metal-complex-based DDS agent, Fe(salen) nanoparticles in a water suspension, 13,14 which proved suitable for magnetic DDS, chemotherapy, magnetic resonance imaging (MRI) and AMF-induced local hyperthermal therapy.…”

“…In other words, the Fe(salen) metal complexes, which have been used in the last few decades as asymmetric catalysts [17][18][19][20] and molecular magnets, 21,22 can be employed as magnetically guided anticancer agents. 13,14 Other molecular magnets have been reported but cannot be practically applied due to the very low critical temperature at which they exhibit positive values of magnetization in response to a room temperature magnetic field. [23][24][25][26] However, Fe(salen) also has some drawbacks, such as poor water solubility, loss of magnetic properties in solvents and potential cytotoxicity when accumulated in organs.…”