The Story of Ferumoxytol: Synthesis Production, Current Clinical Applications, and Therapeutic Potential

Abstract

Ferumoxytol, approved by the U.S. Food and Drug Administration in 2009, is one of the intravenous iron oxide nanoparticles authorized for the treatment of iron deficiency in chronic kidney disease and end‐stage renal disease. With its exceptional magnetic properties, catalytic activity, and immune activity, as well as good biocompatibility and safety, ferumoxytol has gained significant recognition in various biomedical diagnoses and treatments. Unlike most existing reviews on this topic, this review primarily focuses on the recent clinical and preclinical advances of ferumoxytol in disease treatment, spanning anemia, cancer, infectious inflammatory diseases, regenerative medicine application, magnetic stimulation for neural modulation, etc. Additionally, the newly discovered mechanisms associated with the biological effects of ferumoxytol are discussed, including its magnetic, catalytic, and immunomodulatory properties. Finally, the summary and future prospects concerning the treatment and application of ferumoxytol‐based nanotherapeutics are presented.

Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI

“…Moreover, because of the inherent magnetic properties, nanoenzymatic activities and immunomodulatory effects of ferumoxytol, this agent has spurred an array of innovative preclinical therapeutic explorations. These explorations span tumor treatments, immune regulation in sepsis, antimicrobial and anti-inflammatory treatments for dental caries and periodontitis, tissue engineering, and magnetic nerve stimulation aimed at alleviating depression and myocardial infarction, among others [ 23 ].…”

Ultrahigh-Resolution Visualization of Vascular Heterogeneity in Brain Tumors via Magnetic Nanoparticles-Enhanced Susceptibility-Weighted Imaging

“…40,41 Notably, clinical-grade Fe 3 O 4 nanoparticles, such as ferumoxytol, have historically been produced using this method. 42,43 Despite its clinical use, ferumoxytol still suffers from several drawbacks, including poor particle uniformity, complex preparation requirements, and limited sensitivity due to relatively lower relaxivity. 44−46 These factors underscore the significant demand for the development of simple and high-performance Fe 3 O 4 NPs tailored for high-field CE-SWI.…”

“…Currently, a variety of methods such as high-temperature thermal decomposition/thermal injection, solvothermal synthesis, and coprecipitation are employed to prepare and control the properties of Fe 3 O 4 NPs . Among these methods, coprecipitation, known for its simplicity and cost-effectiveness, is particularly favorable for mass production of biocompatible Fe 3 O 4 NPs. , Notably, clinical-grade Fe 3 O 4 nanoparticles, such as ferumoxytol, have historically been produced using this method. , Despite its clinical use, ferumoxytol still suffers from several drawbacks, including poor particle uniformity, complex preparation requirements, and limited sensitivity due to relatively lower relaxivity. − These factors underscore the significant demand for the development of simple and high-performance Fe 3 O 4 NPs tailored for high-field CE-SWI. Here, we meticulously deliberated on factors such as the choice of precursor, synthesis methods, and reaction conditions.…”

Radiomodulating Properties of Superparamagnetic Iron Oxide Nanoparticle (SPION) Agent Ferumoxytol on Human Monocytes: Implications for MRI-Guided Liver Radiotherapy

“…Ferumoxytol (Feraheme ® ) is a carbohydrate-coated ultrasmall SPION agent that is FDA-approved for the treatment of iron deficiency anemia. Because of its clearance through the reticuloendothelial system, ferumoxytol has been recently adopted for off-label clinical use as an MRI contrast agent for clinical imaging of liver parenchyma involving contrast uptake by hepatic macrophages (Kupffer cells) [20,21]. Once intravascularly injected, ferumoxytol nanoparticles stay trapped within hepatic Kupffer cells for several weeks causing T2-weighted signal loss within functionally active liver parenchyma [22].…”