Spindle-like MRI-active europium-doped iron oxide nanoparticles with shape-induced cytotoxicity from simple and facile ferrihydrite crystallization procedure

Abstract

Nanoparticles (NPs) that can provide additional functionality to the nanoagents derived from them, e.g., cytotoxicity or imaging abilities, are in high demand in modern nanotechnology. Here, we report new spindle-like iron oxide nanoparticles doped with Eu³⁺ that feature magnetic resonance imaging (MRI) contrasting properties together with shape-related cytotoxicity (unusual for such low 2.4% Eu content). The NPs were prepared by a novel procedure for doping of iron oxide nanoparticles based on the crystallization of amorphous ferrihydrite in the presence of hydrated europium(III) oxide and were thoroughly characterized. Cytotoxicity of low Eu-doped spindle-like hematite nanoparticles was confirmed by MTT assay and further studied in detail by imaging flow cytometry, optical and electron microscopies. Additionally, enhancement of MRI contrast properties of NPs upon doping with europium was demonstrated. According to the MRI using mice as an animal model and direct inductively coupled plasma mass spectrometry (ICP-MS) ¹⁵³Eu biodistribution measurements, these particles accumulate in the liver and spleen. Therefore, NPs present a novel example of a multimodal component combining magnetic imaging and therapeutic (cytotoxic) abilities for development of theranostic nanoagents.