A Milestone in the Chemical Synthesis of Fe₃O₄ Nanoparticles: Unreported Bulklike Properties Lead to a Remarkable Magnetic Hyperthermia

Abstract

Among iron oxide phases, magnetite (Fe3O4) is often the preferred one for nanotechnological and biomedical applications because of its high saturation magnetization and low toxicity. Although there are several synthetic routes that attempt to reach magnetite nanoparticles (NPs), they are usually referred as “IONPs” (iron oxide NPs) due to the great difficulty in obtaining the monophasic and stoichiometric Fe3O4 phase. Added to this problem is the common increase of size/shape polydispersity when larger NPs (D > 20 nm) are synthesized. An unequivocal correlation between a nanomaterial and its properties can only be achieved by the production of highly homogeneous systems, which, in turn, is only possible by the continuous improvement of synthesis methods. There is no doubt that solving the compositional heterogeneity of IONPs while keeping them monodisperse remains a challenge for synthetic chemistry. Herein, we present a methodical optimization of the iron oleate decomposition method to obtain Fe3O4 single nanocrystals without any trace of secondary phases and with no need of postsynthetic treatment. The average dimension of the NPs, ranging from 20 to 40 nm, has been tailored by adjusting the total volume and the boiling point of the reaction mixture. Mössbauer spectroscopy and DC magnetometry have revealed that the NPs present a perfectly stoichiometric Fe3O4 phase. The high saturation magnetization (93 (2) A·m2/kg at RT) and the extremely sharp Verwey transition (at around 120 K) shown by these NPs have no precedent. Moreover, the synthesis method has been refined to obtain NPs with octahedral morphology and suitable magnetic anisotropy, which significantly improves the magnetic hyperthemia performance. The heating power of properly PEGylated nano-octahedrons has been investigated by AC magnetometry, confirming that the NPs present negligible dipolar interactions, which leads to an outstanding magnetothermal efficiency that does not change when the NPs are dispersed in environments with high viscosity and ionic strength. Additionally, the heat production of the NPs within physiological media has been directly measured by calorimetry under clinically safe conditions, reasserting the excellent adequacy of the system for hyperthermia therapies. To the best of our knowledge, this is the first time that such bulklike magnetite NPs (with minimal size/shape polydispersity, minor agglomeration, and exceptional heating power) are chemically synthesized.

Iron–Gold Nanoflowers: A Promising Tool for Multimodal Imaging and Hyperthermia Therapy

“…These results are in good agreement with the linear response theory model, which predicts that 22 nm spherical NPs should provide the optimal mSLP response [ 22 ]. The significantly higher than expected mSLP values presented by Au@Fe-PEG NPs might be related to a higher effective anisotropy, which, as previously reported, is a crucial parameter for the magnetic HT performance of magnetic nanoparticles [ 59 , 60 ]. Further, mSLP was also tested at lower magnetic field amplitude (304 Gauss), resulting in ≈90 W/g, which is still higher than the one exhibited by other magnetic NPs at comparable magnetic field amplitude and higher frequencies [ 61 ].…”

Size-Tunable Magnetite Nanoparticles from Well-Defined Iron Oleate Precursors

“…The drying step contains two other seemingly innocuous variables that lead to reproducibility issues. Multiple studies have analyzed the impact of drying time and temperature on the metal–carboxylate binding mode distribution from syntheses similar to that of FeOl-1. ,,, Balakrishnan et al observed a diminishing signal from free OA with increased drying times, attributing it in part to the removal of crystal hydrate water . This change in the binding mode distribution led to a dramatic change in the resulting nanoparticles, from 6 to 13 nm for drying times from 5 to 30 days, respectively .…”

“…The two new starting materials, FeOl-2 and -3, are used in one-pot syntheses that selectively target a specific nanoparticle size without the use of an additional solvent, seed-mediated growth, or hot injection . As the OA:Fe ratio decreases, less OA is available to control the nanoparticle shape, resulting in larger, albeit nonspherical, particles (Figure f).…”

“…Even slight variations in phase, morphology, homogeneity, and heterostructure can limit or even negate their functional magnetic capabilities . Especially with iron oxide, these capabilities are vital for optimizing responses in applications such as magnetic hyperthermia, , nanocomposite magnetoresistance, − smart fluids, magnetic particle imaging, − magnetic particle spectroscopy, , and thermometry. , …”

Nanozyme-Based Lateral Flow Immunoassay (LFIA) for Extracellular Vesicle Detection

“…Iron oxide superparamagnetic nanoparticles (Fe 3 O 4 MNPs) have attracted considerable scientific interest due to their superparamagnetic properties, biocompatibility, and non-toxicity, resulting in a wide range of biomedical and technological applications. For example, Fe 3 O 4 MNPs have been applied in energy storage [ 1 ]; tissue engineering [ 2 ]; protein, DNA, and cell separation from samples [ 3 , 4 ]; biosensing [ 5 ]; drug-delivery and -targeting [ 6 , 7 , 8 ]; magnetic resonance imaging (MRI) [ 9 , 10 , 11 ]; and as mediators of heat for cancer therapy (hyperthermia) [ 12 ].…”