Magnetic Tunability via Control of Crystallinity and Size in Polycrystalline Iron Oxide Nanoparticles.

Iron oxide nanoparticles (IONPs) are widely used for biomedical applications due to their unique magnetic properties and biocompatibility. However, the controlled synthesis of IONPs with tunable particle sizes and crystallite/grain sizes to achieve desired magnetic functionalities across single-domain and multi-domain size ranges remains an important challenge. Here, a facile synthetic method is used to produce iron oxide nanospheres (IONSs) with controllable size and crystallinity for magnetic tunability. First, highly crystalline Fe3O4 IONSs (crystallite sizes above 24 nm) having an average diameter of 50 to 400 nm are synthesized with enhanced ferrimagnetic properties. The magnetic properties of these highly crystalline IONSs are comparable to those of their nanocube counterparts, which typically possess superior magnetic properties. Second, the crystallite size can be widely tuned from 37 to 10 nm while maintaining the overall particle diameter, thereby allowing precise manipulation from the ferrimagnetic to the superparamagnetic state. In addition, demonstrations of reaction scale-up and the proposed growth mechanism of the IONSs are presented. This study highlights the pivotal role of crystal size in controlling the magnetic properties of IONSs and offers a viable means to produce IONSs with magnetic properties desirable for wider applications in sensors, electronics, energy, environmental remediation, and biomedicine.

Metal-Organic Framework as a New Type of Magnetothermally-Triggered On-Demand Release Carrier.

The development of external stimuli-controlled payload systems has been sought after with increasing interest toward magnetothermally-triggered drug release (MTDR) carriers due to their non-invasive features. However, current MTDR carriers present several limitations, such as poor heating efficiency caused by the aggregation of iron oxide nanoparticles (IONPs) or the presence of antiferromagnetic phases which affect their efficiency. Herein, a novel MTDR carrier is developed using a controlled encapsulation method that fully fixes and confines IONPs of various sizes within the metal-organic frameworks (MOFs). This novel carrier preserves the MOF's morphology, porosity, and IONP segregation, while enhances heating efficiency through the oxidation of antiferromagnetic phases in IONPs during encapsulation. It also features a magnetothermally-responsive nanobrush that is stimulated by an alternating magnetic field to enable on-demand drug release. The novel carrier shows improved heating, which has potential applications as contrast agents and for combined chemo and magnetic hyperthermia therapy. It holds a great promise for magneto-thermally modulated drug dosing at tumor sites, making it an exciting avenue for cancer treatment.

Competing Magnetic Interactions and Field-Induced Metamagnetic Transition in Highly Crystalline Phase-Tunable Iron Oxide Nanorods.

The inherent existence of multi phases in iron oxide nanostructures highlights the significance of them being investigated deliberately to understand and possibly control the phases. Here, the effects of annealing at 250 °C with a variable duration on the bulk magnetic and structural properties of high aspect ratio biphase iron oxide nanorods with ferrimagnetic Fe3O4 and antiferromagnetic α-Fe2O3 are explored. Increasing annealing time under a free flow of oxygen enhanced the α-Fe2O3 volume fraction and improved the crystallinity of the Fe3O4 phase, identified in changes in the magnetization as a function of annealing time. A critical annealing time of approximately 3 h maximized the presence of both phases, as observed via an enhancement in the magnetization and an interfacial pinning effect. This is attributed to disordered spins separating the magnetically distinct phases which tend to align with the application of a magnetic field at high temperatures. The increased antiferromagnetic phase can be distinguished due to the field-induced metamagnetic transitions observed in structures annealed for more than 3 h and was especially prominent in the 9 h annealed sample. Our controlled study in determining the changes in volume fractions with annealing time will enable precise control over phase tunability in iron oxide nanorods, allowing custom-made phase volume fractions in different applications ranging from spintronics to biomedical applications.

Emergent magnetism and exchange bias effect in iron oxide nanocubes with tunable phase and size.

We report a systematic investigation of the magnetic properties including the exchange bias (EB) effect in an iron oxide nanocube system with tunable phase and average size (10, 15, 24, 34, and 43 nm). X-ray diffraction and Raman spectroscopy reveal the presence of Fe3O4, FeO, andα-Fe2O3phases in the nanocubes, in which the volume fraction of each phase varies depending upon particle size. While the Fe3O4phase is dominant in all and tends to grow with increasing particle size, the FeO phase appears to coexist with the Fe3O4phase in 10, 15, and 24 nm nanocubes but disappears in 34 and 43 nm nanocubes. The nanocubes exposed to air resulted in anα-Fe2O3oxidized surface layer whose thickness scaled with particle size resulting in a shell made ofα-Fe2O3phase and a core containing Fe3O4or a mixture of both Fe3O4and FeO phases. Magnetometry indicates that the nanocubes undergo Morin (of theα-Fe2O3phase) and Verwey (of the Fe3O4phase) transitions at ∼250 K and ∼120 K, respectively. For smaller nanocubes (10, 15, and 24 nm), the EB effect is observed below 200 K, of which the 15 nm nanocubes showed the most prominent EB with optimal antiferromagnetic (AFM) FeO phase. No EB is reported for larger nanocubes (34 and 43 nm). The observed EB effect is ascribed to the strong interfacial coupling between the ferrimagnetic (FiM) Fe3O4phase and AFM FeO phase, while its absence is related to the disappearance of the FeO phase. The Fe3O4/α-Fe2O3(FiM/AFM) interfaces are found to have negligible influence on the EB. Our findings shed light on the complexity of the EB effect in mixed-phase iron oxide nanosystems and pave the way to design exchange-coupled nanomaterials with desirable magnetic properties for biomedical and spintronic applications.

Spin Seebeck Effect in Iron Oxide Thin Films: Effects of Phase Transition, Phase Coexistence, And Surface Magnetism.

Understanding the effects of phase transition, phase coexistence, and surface magnetism on the longitudinal spin Seebeck effect (LSSE) in a magnetic system is essential to manipulate the spin to charge current conversion efficiency for spincaloritronic applications. We aim to elucidate these effects by performing a comprehensive study of the temperature dependence of the LSSE in biphase iron oxide (BPIO = α-Fe2O3 + Fe3O4) thin films grown on Si (100) and Al2O3 (111) substrates. A combination of a temperature-dependent anomalous Nernst effect (ANE) and electrical resistivity measurements show that the contribution of the ANE from the BPIO layer is negligible in comparison to the intrinsic LSSE in the Si/BPIO/Pt heterostructure, even at room temperature. Below the Verwey transition of the Fe3O4 phase, the total signal across BPIO/Pt is dominated by the LSSE. Noticeable changes in the intrinsic LSSE signal for both Si/BPIO/Pt and Al2O3/BPIO/Pt heterostructures around the Verwey transition of the Fe3O4 phase and the antiferromagnetic (AFM) Morin transition of the α-Fe2O3 phase are observed. The LSSE signal for Si/BPIO/Pt is found to be almost 2 times greater than that for Al2O3/BPIO/Pt; however, an opposite trend is observed for the saturation magnetization. Magnetic force microscopy reveals the higher density of surface magnetic moments of the Si/BPIO film in comparison to the Al2O3/BPIO film, which underscores the dominant role of interfacial magnetism on the LSSE signal and thereby explains the larger LSSE for Si/BPIO/Pt.

Multifunctional nanocarriers of Fe3O4@PLA-PEG/curcumin for MRI, magnetic hyperthermia and drug delivery.

Background: Despite medicinal advances, cancer is still a big problem requiring better diagnostic and treatment tools. Magnetic nanoparticle (MNP)-based nanosystems for multiple-purpose applications were developed for these unmet needs. Methods: This study fabricated novel trifunctional MNPs of Fe3O4@PLA-PEG for drug release, MRI and magnetic fluid hyperthermia. Result: The MNPs provided a significant loading of curcumin (∼11%) with controllable release ability, a high specific absorption rate of 82.2 W/g and significantly increased transverse relaxivity (r2 = 364.75 mM-1 s-1). The in vivo study confirmed that the MNPs enhanced MRI contrast in tumor observation and low-field magnetic fluid hyperthermia could effectively reduce the tumor size in mice bearing sarcoma 180. Conclusion: The nanocarrier has potential for drug release, cancer treatment monitoring and therapy.

In this study, the authors designed and fabricated novel magnetic trifunctional nanoparticles of Fe₃O₄@PLA-PEG. The 8.5 nm Fe₃O₄ core was covered with the polymeric matrix of PLA-PEG to encapsulate an anticancer agent of curcumin at a content of about 11%. Curcumin release from the nanoparticles (NPs) could be controlled by applying a remote alternating magnetic field. The NPs enhanced MRI contrast, which allowed the authors to better distinguish the tumor and surroundings in MR images, which would help monitor treatment. The heat that NPs generated when applied to a field at low intensity could effectively reduce the tumor size in mice bearing sarcoma 180. The nanocarrier, therefore, has potential for cancer treatment monitoring and drug release conjuvant with magnetic hyperthermia therapy.

Iron Oxide Nanorings and Nanotubes for Magnetic Hyperthermia: The Problem of Intraparticle Interactions.

Magnetic interactions can play an important role in the heating efficiency of magnetic nanoparticles. Although most of the time interparticle magnetic interactions are a dominant source, in specific cases such as multigranular nanostructures intraparticle interactions are also relevant and their effect is significant. In this work, we have prepared two different multigranular magnetic nanostructures of iron oxide, nanorings (NRs) and nanotubes (NTs), with a similar thickness but different lengths (55 nm for NRs and 470 nm for NTs). In this way, we find that the NTs present stronger intraparticle interactions than the NRs. Magnetometry and transverse susceptibility measurements show that the NTs possess a higher effective anisotropy and saturation magnetization. Despite this, the AC hysteresis loops obtained for the NRs (0-400 Oe, 300 kHz) are more squared, therefore giving rise to a higher heating efficiency (maximum specific absorption rate, SARmax = 110 W/g for the NRs and 80 W/g for the NTs at 400 Oe and 300 kHz). These results indicate that the weaker intraparticle interactions in the case of the NRs are in favor of magnetic hyperthermia in comparison with the NTs.

Isolation of Cancer-Derived Exosomes Using a Variety of Magnetic Nanostructures: From Fe3O4 Nanoparticles to Ni Nanowires.

Isolating and analyzing tumor-derived exosomes (TEX) can provide important information about the state of a tumor, facilitating early diagnosis and prognosis. Since current isolation methods are mostly laborious and expensive, we propose herein a fast and cost-effective method based on a magnetic nanoplatform to isolate TEX. In this work, we have tested our method using three magnetic nanostructures: (i) Ni magnetic nanowires (MNWs) (1500 × 40 nm), (ii) Fe3O4 nanorods (NRs) (41 × 7 nm), and (iii) Fe3O4 cube-octahedral magnetosomes (MGs) (45 nm) obtained from magnetotactic bacteria. The magnetic response of these nanostructures has been characterized, and we have followed their internalization inside canine osteosarcoma OSCA-8 cells. An overall depiction has been obtained using a combination of Fluorescence and Scanning Electron Microscopies. In addition, Transmission Electron Microscopy images have shown that the nanostructures, with different signs of degradation, ended up being incorporated in endosomal compartments inside the cells. Small intra-endosomal vesicles that could be precursors for TEX have also been identified. Finally, TEX have been isolated using our magnetic isolation method and analyzed with a Nanoparticle tracking analyzer (NanoSight). We observed that the amount and purity of TEX isolated magnetically with MNWs was higher than with NRs and MGs, and they were close to the results obtained using conventional non-magnetic isolation methods.

Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents.

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.

Photopolymerization-based synthesis of iron oxide nanoparticle embedded PNIPAM nanogels for biomedical applications.

Conventional therapeutic techniques treat patients by delivering biotherapeutics to the entire body. With targeted delivery, biotherapeutics are transported to the afflicted tissue reducing exposure to healthy tissue. Targeted delivery devices are minimally composed of a stimuli responsive polymer allowing triggered release and magnetic nanoparticles enabling targeting as well as alternating magnetic field (AMF) heating. Although more traditional methods, like emulsion polymerization, have been used to realize such devices, the synthesis is problematic. For example, surfactants preventing agglomeration must be removed from the product increasing time and cost. Ultraviolet (UV) photopolymerization is more efficient and ensures safety by using biocompatible substances. Reactants selected for nanogel fabrication were N-isopropylacrylamide (monomer), methylene bis-acrylamide (crosslinker), and Irgacure 2959 (photoinitiator). The 10 nm superparamagnetic nanoparticles for encapsulation were composed of iron oxide. Herein, a low-cost, scalable, and rapid, custom-built UV photoreactor with in situ, spectroscopic monitoring system is used to observe synthesis. This method also allows in situ encapsulation of the magnetic nanoparticles simplifying the process. Nanogel characterization, performed by transmission electron microscopy, reveals size-tunable nanogel spheres between 40 and 800 nm in diameter. Samples of nanogels encapsulating magnetic nanoparticles were subjected to an AMF and temperature increase was observed indicating triggered release is possible. Results presented here will have a wide range of applications in medical sciences like oncology, gene delivery, cardiology, and endocrinology.

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems.

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and related phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.

Transverse susceptibility as a biosensor for detection of Au-Fe3O4 nanoparticle-embedded human embryonic kidney cells.

We demonstrate the possibility of using a radio-frequency transverse susceptibility (TS) technique based on a sensitive self-resonant tunnel-diode oscillator as a biosensor for detection of cancer cells that have taken up magnetic nanoparticles. This technique can detect changes in frequency on the order of 10 Hz in 10 MHz. Therefore, a small sample of cells that have taken up nanoparticles when placed inside the sample space of the TS probe can yield a signal characteristic of the magnetic nanoparticles. As a proof of the concept, Fe3O4 nanoparticles coated with Au (mean size ~60 nm) were synthesized using a micellar method and these nanoparticles were introduced to the medium at different concentrations of 0.05, 0.1, 0.5, and 1 mg/mL buffer, where they were taken up by human embryonic kidney (HEK) cells via phagocytosis. While the highest concentration of Au-Fe3O4 nanoparticles (1 mg/mL) was found to give the strongest TS signal, it is notable that the TS signal of the nanoparticles could still be detected at concentrations as low as 0.1 mg/mL.