Tuning the Morphological Appearance of Iron(III) Fumarate: Impact on Material Characteristics and Biocompatibility

Iron­(III) fumarate materials are well suited for biomedical applications as they feature biocompatible building blocks, porosity, chemical functionalizability, and magnetic resonance imaging (MRI) activity. The synthesis of these materials however is difficult to control, and it has been challenging to produce monodisperse particle sizes and morphologies that are required in medical use. Here, we report the optimization of iron­(III) fumarate nano- and microparticle synthesis by surfactant-free methods, including room temperature, solvothermal, microwave, and microfluidic conditions. Four variants of iron­(III) fumarate with distinct morphologies were isolated and are characterized in detail. Structural characterization shows that all iron­(III) fumarate variants exhibit the metal–organic framework (MOF) structure of MIL-88A. Nanoparticles with a diameter of 50 nm were produced, which contain crystalline areas not exceeding 5 nm. Solvent-dependent swelling of the crystalline particles was monitored using in situ X-ray diffraction. Cytotoxicity experiments showed that all iron­(III) fumarate variants feature adequate biotolerability and no distinct interference with cellular metabolism at low concentrations. Magnetic resonance relaxivity studies using clinical MRI equipment, on the other hand, proved that the MRI contrast characteristics depend on particle size and morphology. All in all, this study demonstrates the possibility of tuning the morphological appearance of iron­(III) fumarate particles and illustrates the importance of optimizing synthesis conditions for the development of new biomedical materials.