Maltol‐Functionalized Fe₃O₄ Nanoparticles as T₂ Magnetic Resonance Imaging Contrast Agents

Abstract

We present the use of maltol (3‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one) as a capping ligand for iron oxide nanomaterials. Water‐soluble maltol‐coated Fe3O4 nanoparticles were synthesized by a reductive one‐pot synthesis. The nanoparticles were found to be stable in water, and their superparamagnetic properties enabled their application as ultrahigh field T2 magnetic resonance imaging (MRI) contrast agents. High r2 relaxivity and r2/r1 ratios were determined at clinical (B0 = 3 T) and ultrahigh (B0 = 9.4 T) fields, making them on par or superior to current iron‐oxide based commercial MRI contrast agents. A low cytotoxic response in three distinct cell types (HUVEC, KB, U343) indicate maltol‐coated Fe3O4 nanoparticles are promising T2 MRI contrast agents.

Synthesis, characterization, and evaluation of PEGylated first-row transition metal ferrite nanoparticles as T2contrast agents for high-field MRI

“…This synthesis was inspired by a reductive synthesis of Fe 3 O 4 NPs. 30,41 In the initial report, 41 Yathindranath et al describe a reductive step to form the divalent Fe 2+ cations necessary for the formation of the spinel structure. In our case, no such reductive step is required as the divalent cation is directly supplied.…”

“…This difficulty is exacerbated by signicant dependencies of magnetic relaxivities on the magnetic eld strength, 66 the nature of the solvent (i.e., water vs. plasma vs. buffer), the surface coating, 30,39 aggregation, 56 and magnetic dynamics.…”

“…Well-know examples include the commercially available Ferridex® and Combidex®. Ferridex® has r 2 ¼ 120 mM À1 s À1 at a magnetic eld of 1.5 T, while the r 2 /r 1 increases from 10.1 to 22 when increasing the magnetic eld from 1.5 to 3.0 T. 30 Similarly, Combidex® has r 2 ¼ 65 mM…”

“…Recently, we showed that maltol, an FDA-approved pharmaceutical additive that enhances the bioavailability of iron in vivo, is a suitable capping agent for obtaining efficient T 2 contrast agents at both clinical and high elds with demonstrated inertness to human cell lines. 30 It is to be noted that direct incorporation of a molecular (as opposed to a polymeric) capping agent on the NP surface during the formative stage may call for milder synthetic conditions to maintain the integrity of the capping agent, which may lead to reduced phase purity and magnetic behaviour of the ferrite nanocrystals formed. To avoid this, a two-stage synthesis is oen used, initially generating a hydrophobic NP surface under harsher reaction conditions, which is then subjected to a post-synthetic ligand exchange regime, in order to render the NPs water soluble.…”

Functionalizable composite nanoparticles as a dual magnetic resonance imaging/computed tomography contrast agent for medical imaging

“…In the literature, the T 2 relaxivity of Fe 3 O 4 nanoparticles used as a contrast agent has been reported to be in the range of 80–120 m M −1 s −1 . However, these literature values are for Fe 3 O 4 particles without a shell.…”