Ferrimagnetic Iron Oxide Research Articles

Intracellular Magnetic Hyperthermia Sensitizes Sorafenib to Orthotopic Hepatocellular Carcinoma Via Amplified Ferroptosis.

Sorafenib (SRF) is recognized as the primary treatment for hepatocellular carcinoma (HCC), yet the emergence of SRF resistance in many HCC patients results in unfavorable outcomes. Enhancing the efficacy of SRF in HCC remains a significant challenge. SRF works in inducing ferroptosis, a form of cell death, in cancer cells through the inhibition of glutathione peroxidase 4 (GPX4). The effectiveness of this process is limited by the low levels of cellular iron and reactive oxygen species (ROS). A promising approach to circumvent this limitation is the use of intracellular magnetic hyperthermia (MH) mediated by magnetic iron oxide nanomaterials (MIONs). When MIONs are subjected to an alternating magnetic field (AMF), they heat up, enhancing the Fenton reaction, which in turn significantly increases the production of ROS within cells. In this study, we explore the capability of MH facilitated by high-performance ferrimagnetic vortex-domain iron oxide nanoring (FVIO) to enhance the effectiveness of SRF treatment in HCC. The increased iron uptake facilitated by FVIO significantly enhances the sensitivity of HCC cells to SRF-induced ferroptosis. Moreover, the nanoheat generated by FVIO in response to an AMF further elevates ROS levels and stimulates lipid hydroperoxide (LPO) production and GPX4 inactivation, thereby intensifying ferroptosis. Both in vitro and in vivo animal studies demonstrate that combining FVIO-mediated MH with SRF significantly reduces cell viability and inhibits tumor growth, primarily through enhanced ferroptosis, with minimal side effects. The effectiveness of this combination therapy is affected by the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine (DFO). The combination treatment of FVIO-mediated MH and SRF offers a strategy for HCC treatment by promoting accelerated ferroptosis, presenting a different perspective for the development of ferroptosis-based anticancer therapies.

Reprogrammed IDO-Induced Immunosuppressive Microenvironment Synergizes with Immunogenic Magnetothermodynamics for Improved Cancer Therapy.

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.

Influence of magnetic interactions in iron oxide nanoparticle polymer composites on magnetism and induction heating

Induction heating of composite materials is of great interest in fields such as controlled polymer curing or degradation, self-healing or contactless joining. Ferrimagnetic iron oxide nanoparticle (IONPs) are suitable candidates for a powder additive to provide this inductive heating functionality, while being low-cost, abundant and a well-studied material class. Varying IONP size, morphology or doping facilitates fine-tuning of their heating properties. However, the interactions of such IONP additives in material composites are often neglected and can significantly alter the induction heating mechanism. In this work, we systematically vary the IONP interactions in polydimethylsiloxane composite materials by integrating 1.) dispersed IONPs 2.) supraparticles of IONPs (micrometer-assemblies), and 3.) oven-dried hard agglomerated IONPs. Additionally, these three levels of interaction are investigated for three different IONPs types (dodecahedrally and octahedrally shaped, as well as cobalt-doped). In general, dispersed IONPs reveal a broader hysteresis and therefore a faster heating curve. We highlight that not only IONP characteristics (size, morphology, doping), but also excitation field strength and foremost IONP interactions in the composite materials are parameters that are interdependent regarding induction heating and need to be considered as such for optimization in an application-oriented scenario.

Synthesis of 2D-Material(G,GO,rGO,h-BN)-Magnetic(Fe,Fe3O4)Nanocomposites

For the purpose of synthesizing 2D-Material–Magnetic nanocomposites, several new modifications of existing 2D-materials synthesis methods by exfoliation and chemical synthesis from liquid charge are developed. Using them, graphene (G), graphene oxide (GO), reduced graphene oxide (rGO) and hexagonal boron nitride (h-BN) matrix magnetic nanocomposites for the first time are obtained by coating or intercalation their nanoparticles with ferromagnetic iron (Fe) or ferrimagnetic iron oxide – magnetite (Fe3O4). These materials are prospective for variety of high tech applications. In particular, h-BN–Fe3O4 composite nanoparticles can serve for neutron-capturing boron isotope 10B effective delivery agents in BNCT (Boron Neutron Capture Therapy) of cancer as they allow the controlling by an external magnetic field targeting to tumor tissue.

Impact of Nanoheater Subcellular Localization on the Antitumor Immune Efficacy of Magnetic Hyperthermia

Magnetic nanoparticles (MNPs)-mediated magnetic hyperthermia therapy is garnering attention as a promising modality for tumor remission. This therapy combines localized nano-scale heating and reactive oxygen species-related immunologic effects. A critical aspect in optimizing this therapy involves understanding how nanoheaters’ subcellular localizations influence the therapeutic efficacy and immunological effects of magnetic hyperthermia. Herein, we investigate these effects by focusing on the strategic localization of ferrimagnetic vortex-domain iron oxide (FVIO) nanorings within lysosomes and the cytoplasm of hepatocellular carcinoma (HCC) cells. The comparative analysis revealed that lysosomal-localized magnetic hyperthermia markedly increased apoptosis in Hepa1–6 cells and effectively induced immunogenic cell death (ICD). Mechanistically, lysosomal-localized magnetic hyperthermia led to Bid-associated apoptosis and caspase-1-dependent interleukin-1β (IL-1β) secretion, likely due to enhanced lysosomal membrane permeabilization. Moreover, it reduced calreticulin degradation and increased its presence at the cell membrane, thereby boosting ICD efficiency. In contrast, cytoplasmic-localized magnetic hyperthermia showed comparatively lesser impact than its lysosomal-localized counterpart. In vivo experiments reinforced the exceptional efficacy of lysosomal-localized magnetic hyperthermia, which notably enhanced dendritic cells activation and T cells infiltration in both tumors and lymph nodes, thereby triggering a robust antitumor immune response. Additionally, lysosomal-localized magnetic hyperthermia improved tumor vaccine efficacy and demonstrated the potential for sustaining long-term immune responses in antitumor treatments. This study highlights the crucial role of subcellular positioning of magnetic nanoheaters in determining the efficacy of antitumor immunological responses in magnetic hyperthermia therapy, offering valuable insights for future cancer treatment strategies.

Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.

Single-cell transcriptomics reveals ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia exerts antitumor effects by alleviating macrophage suppression in breast cancer

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages’ phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell–cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.

Amino-grafted water-soluble ferrimagnetic iron oxide nanoparticles with ultra-high relaxivity for dual-modal magnetic resonance imaging

Highly stable dispersion is an important precondition for functionalized magnetic nanoparticles used as a contrast agent. Amino-grafted ferromagnetic γ-Fe2O3 nanoparticles are synthesized by deep-eutectic-solvent electrolysis for magnetic resonance imaging. The statistical naked scale of the particle is 8.2 nm with a magnetization of 71.9 emu g−1. An ultra-high Zeta potential of + 50 mV boosts the dispersion stable for more than 600 days, which is unprecedented. The 26.4 nm hydrated nanoparticles exhibit high biocompatibility after being efficiently ingested by cells in vitro. Both longitudinal relaxation efficiency of 179.7 mM−1 s−1 and transverse relaxivity of 497.8 mM−1 s−1 are among the highest demonstrated in recent years. Whether in vitro or in vivo, the imaging mode changes from T1 to T2 with the increase of iron equivalent. At doses 0.12 and 0.91 mg Fe per kg living body, the nanoparticles are capable of prominently weighted imaging of T1 and T2 of the liver, respectively. The nanocrystals can significantly distinguish between normal tissue and the tumor site of the liver as well. Findings demonstrate that the highly stable dispersion of amino-grafted ferrimagnetic nanoparticles is capable of dual-modal magnetic resonance imaging with high relaxation efficiency and significant resolution.

Mineral magnetic properties of urban forest soils tailored to soil quality indicator

Ecosystem surveys reveal the benefits to society, provided by the natural environment, which in turn is chiefly regulated by the geodiversity. Thus, physico-chemical processes regulating the solid rock/sediment response to environmental changes comprise an important part in the assessment of natural ecosystems. Environmental magnetism provides a wide set of field and laboratory data able to discover natural and anthropogenic processes affecting different environmental compartments. Despite this, geosciences and environmental magnetism in particular, are under-represented in ecosystem assessment tools due to the lack of unified and clearly articulated application template. In this study, we propose a new mineral magnetic indicator of soil’s quality, based on detailed appraisal of field- and laboratory mineral magnetic characteristics of a collection of 453 urban topsoil samples. Field magnetic susceptibility (Kfield) and laboratory measurements of magnetic parameters revealed that soil magnetism reflects sensitively soils affected by vehicle traffic and park’s alleys foot load from semi-natural soil. Geochemical analyses of the content of Potentially Toxic Elements (PTEs) on a sub-set of samples was used for magnetic data validation. Correlation analysis showed strong positive link between magnetic parameters and the main PTEs, the strongest being obtained between magnetic susceptibility and the complex pollution load index (PLI). Factor analysis suggested that three factors account for the 74% of data variability. They were assigned to: 1) traffic emissions, 2) pedogenic contribution and 3) lithogenic input plus anthropogenic organic waste additions. Novel mineral magnetic Indicator (MAG) was defined, combining information on composition, concentration and grain size of ferrimagnetic iron oxides, using scored contributions from five magnetic parameters and grain size sensitive ratios. Evaluation of the spatial MAG map showed its suitability as a complex indicator of soils’ contamination with PTEs. Kfield reflected sensitively overall anthropogenic load not necessarily related to PTEs contamination but also to foot trampling and application of fertilizers.

Spin-Selective Oxygen Evolution Reaction in Chiral Iron Oxide Nanoparticles: Synergistic Impact of Inherent Magnetic Moment and Chirality.

Electron spin polarization is identified as a promising avenue for enhancing the oxygen evolution reaction (OER), which is the bottleneck that limits the energy efficiency of water-splitting. Here, we report that both ferrimagnetic (f-Fe3O4) and superparamagnetic iron oxide (s-Fe3O4) catalysts can exhibit external magnetic field (Hext)-induced OER enhancement, and the activity is proportional to their intrinsic magnetic moment. Additionally, the chirality-induced spin selectivity (CISS) effect was utilized in synergy with Hext to get a maximum enhancement of up to 89% improvement in current density (at 1.8 V vs RHE) with a low onset potential of 270 mV in s-Fe3O4 catalysts. Spin polarization and the resultant spin selectivity suppress the production of H2O2 and promote the formation of ground state triplet O2 during the OER. Furthermore, the design of chiral s-Fe3O4 with synergistic spin potential effect demonstrates a high spin polarization of ∼42%, as measured using conductive atomic force microscopy (c-AFM).

Reversal of HMGA1-Mediated Immunosuppression Synergizes with Immunogenic Magnetothermodynamic for Improved Hepatocellular Carcinoma Therapy.

Magnetothermodynamic (MTD) therapy can activate antitumor immune responses by inducing potent immunogenic tumor cell death. However, tumor development is often accompanied by multifarious immunosuppressive mechanisms that can counter the efficacy of immunogenic MTD therapy. High-mobility group protein A1 (HMGA1) is overexpressed within hepatocellular carcinoma tissues and plays a crucial function in the generation of immunosuppressive effects. The reversal of HMGA1-mediated immunosuppression could enhance immunogenic tumor cell death-induced immune responses. A ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-based nanovehicle was developed, which is capable of efficiently mediating an alternating magnetic field for immunogenic tumor cell death induction, while concurrently delivering HMGA1 small interfering (si)RNA (siHMGA1) to the cytoplasm of hepatocellular carcinoma Hepa 1-6 cells for HMGA1 pathway interference. Using siHMGA1-FVIO-mediated MTD therapy, the proliferation of hepatocellular carcinoma Hepa 1-6 tumors was inhibited, and the survival of a mouse model was improved. We also demonstrated that siHMGA1-FVIO-mediated MTD achieved synergistic antitumor effects in a subcutaneous hepatocellular carcinoma Hepa 1-6 and H22 tumor model by promoting dendritic cell maturation, enhancing antigen-presenting molecule expression (both major histocompatibility complexes I and II), improving tumor-infiltrating T lymphocyte numbers, and decreasing immunosuppressive myeloid-derived suppressor cells, interleukin-10, and transforming growth factor-β expression. The nanoparticle system outlined in this paper has the potential to target HMGA1 and, in combination with MTD-induced immunotherapy, is a promising approach for hepatocellular carcinoma treatment.

Penetrative and Sustained Drug Delivery Using Injectable Hydrogel Nanocomposites for Postsurgical Brain Tumor Treatment

Postsurgical treatment of glioblastoma multiforme (GBM) by systemic chemotherapy and radiotherapy is often inefficient. Tumor cells infiltrating deeply into the brain parenchyma are significant obstacles to the eradication of GBM. Here, we present a potential solution to this challenge by introducing an injectable thermoresponsive hydrogel nanocomposite. As a liquid solution that contains drug-loaded micelles and water-dispersible ferrimagnetic iron oxide nanocubes (wFIONs), the hydrogel nanocomposite is injected into the resected tumor site after surgery. It promptly gelates at body temperature to serve as a soft, deep intracortical drug reservoir. The drug-loaded micelles target residual GBM cells and deliver drugs with a minimum premature release. Alternating magnetic fields accelerate diffusion through heat generation from wFIONs, enabling penetrative drug delivery. Significantly suppressed tumor growth and improved survival rates are demonstrated in an orthotopic mouse GBM model. Our system proves the potential of the hydrogel nanocomposite platform for postsurgical GBM treatment.

Thermosensitivity through Exchange Coupling in Ferrimagnetic/Antiferromagnetic Nano-Objects for Magnetic-Based Thermometry.

Temperature is a fundamental physical quantity important to the physical and biological sciences. Measurement of temperature within an optically inaccessible three-dimensional (3D) volume at microscale resolution is currently limited. Thermal magnetic particle imaging (T-MPI), a temperature variant of magnetic particle imaging (MPI), hopes to solve this deficiency. For this thermometry technique, magnetic nano-objects (MNOs) with strong temperature-dependent magnetization (thermosensitivity) around the temperature of interest are required; here, we focus between 200 K and 310 K. We demonstrate that thermosensitivity can be amplified in MNOs consisting of ferrimagnetic (FiM) iron oxide (ferrite) and antiferromagnetic (AFM) cobalt oxide (CoO) through interface effects. The FiM/AFM MNOs are characterized by X-ray diffraction (XRD), (scanning) transmission electron microscopy (STEM/TEM), dynamic light scattering (DLS), and Raman spectroscopy. Thermosensitivity is evaluated and quantified by temperature-dependent magnetic measurements. The FiM/AFM exchange coupling is confirmed by field-cooled (FC) hysteresis loops measured at 100 K. Magnetic particle spectroscopy (MPS) measurements were performed at room temperature to evaluate the MNOs MPI response. This initial study shows that FiM/AFM interfacial magnetic coupling is a viable method to increase thermosensitivity in MNOs for T-MPI.

Abstract TP241: Therapeutic Effects Of Magnet-induced Stem Cells Using Ferrimagnetic Iron Oxide Nanoparticles In Ischemic Stroke Model

Background: The efficiency of targeted delivery of stem cells via transplantation by intravenous injection is limited because of rapid clearance. Thus, more effective, newer methods are required. We hypothesized that combining the use of ferrimagnetic iron oxide nanoparticles (FION) labeling and magnetic fields could enhance the targeted delivery of stem cells after ischemic stroke. Methods: In a typical synthesis of FION nanocubes, iron(III) acetylacetonate was added to a mixture of oleic acid, 4-biphenylcarboxylic acid, and benzyl ether. Therapeutic effects of neural stem cells (NSC) using the magnetic nanoparticles in the cerebral ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was induced in SD-rats. Iron oxide nanoparticle-labeled NSCs were injected into the tail vein. Magnetic resonance tracking and confirming labeled stem cells with Prussian blue staining. Polypeptides derived from receptors for advanced glycation end products and pharmaceutical composition for preventing and treating cerebrovascular disease comprise the same. Results: In the F3-VEGF NSC cell, FION uptake was shown as immunofluorescence. After overexpression of VEGF in F3 cells, it was confirmed by Western blotting. The measurements of cytotoxicity in FION's NSC showed toxicity over 80g but 40g was treated for 7 days and was not toxic. Six hours after MCAO induction, 4x10 6 NSCs were injected, and a magnet hat so that the stem cells implanted in the pathogen could move well. After one day, a behavioral test was conducted every week for up to 35 days. After MCAO induction, the group transplanted with FION-NSCs significantly improved in the behavioral test on Day 35 compared to the control group. In order to measure the distribution of FION in tissue, MRI was performed showing penetrating into the lesions of the white circles. As a result of ICP-MS, the magnet-applioed group was concentrated with FION 7 times more compared with the FION-only group. The distribution in brain tissue was observed through FION's Fluorescence images. Conclusions: Our study suggests that this use of a magnetic field may be useful for improving the efficacy of targeted migration of stem cells in stem-based cell therapy in ischemic brain injury.

Bioinformatics Analysis of Protein Homologues of Magnetotactic Bacteria Magnetosome Island Proteins in Human Proteome

Background. The number of biogenic magnetic nanoparticles (BMN), present in human organs and tissues in the form of magnetite (ferrimagnetic iron oxide), increases in oncological and neurodegenerative diseases. Therefore, the study of homologues of BMN biomineralization proteins (mam-proteins) of magnetotaxis bacteria (MTB) in human proteome is relevant task. This concern is due primarily to the expediency of establishing patterns of changes in the expression of these proteins and searching for correlations with oncological and neurodegenerative diseases. Objective. We are aimed to conduct the bioinformatic analysis of homologues of MTB mam-proteins in humans and to determine the patterns of changes in the expression of these proteins, as well as to search for their connections with the specified diseases. This will allow to identify the main candidate proteins (among the known homologues of MTB mam-proteins in humans) for experimental verification of their participation in the genetically programmed mechanism of BMN biosynthesis in humans. Methods. The methods of comparative genomics were used, in particular the BLAST (Basic Local Alignment Search Tool) program of the NCBI database. Database tools were also used: NCBI Conserved Domain Search, The Cancer Genome Atlas database, Ensembl database. Results. The bioinformatic analysis of 16 homologues of MTB mam-proteins in humans was carried out, namely: PEX5, ANAPC7, CDC23, CDC27 and SGTA – homologues of MamA in MTB; SLC30A4, SLC30A9, SLC39A3 and SLC39A4 – homologs of MamB and MamM in MTB; HTRA1, HTRA2, HTRA3 and HTRA4 – MamO and MamE homologues in MTB; SCRIB, PDZK1 and PDZD3 – MamE homologues in MTB. Using pairwise alignments, the degree of homology between the mam-proteins of the MTB magnetosome island and the corresponding human proteins was determined, conserved domains and their functions were determined, changes in their expression levels in cancer and normal conditions were determined by analyzing the relevant databases, and the metabolic pathways to which the data proteins are involved were analysed. The analysis of the obtained data allowed to assume the presence of the main homologues of the MTB mam-proteins of the magnetosome island in humans, which cause an increase in the level of BMN in oncological and neurodegenerative diseases, namely: an increase in the expression level of the proteins PEX5, ANAPC7 (homologs of MamA), SLC39A3, SLC39A4 (homologs of MamB and MamM), HTRA4 (MamO and MamE homolog) and SCRIB (MamE homolog). Conclusions. The obtained data allow us to assume that the proteins PEX5, ANAPC7, SGTA, SLC39A3, SLC39A4, HTRA4 and SCRIB are the main homologues of the MTB mam-proteins in humans and cause an increase in the level of BMN in oncological and neurodegenerative diseases.

Biocompatible Iron Oxide Nanoring-Labeled Mesenchymal Stem Cells: An Innovative Magnetothermal Approach for Cell Tracking and Targeted Stroke Therapy.

Labeling stem cells with magnetic nanoparticles is a promising technique for in vivo tracking and magnetic targeting of transplanted stem cells, which is critical for improving the therapeutic efficacy of cell therapy. However, conventional endocytic labeling with relatively poor labeling efficiency and a short labeling lifetime has hindered the implementation of these innovative enhancements in stem-cell-mediated regenerative medicine. Herein, we describe an advanced magnetothermal approach to label mesenchymal stem cells (MSCs) efficiently by local induction of heat-enhanced membrane permeability for magnetic resonance imaging (MRI) tracking and targeted therapy of stroke, where biocompatible γ-phase, ferrimagnetic vortex-domain iron oxide nanorings (γ-FVIOs) with superior magnetoresponsive properties were used as a tracer. This approach facilitates a safe and efficient labeling of γ-FVIOs as high as 150 pg of Fe per cell without affecting the MSCs proliferation and differentiation, which is 3.44-fold higher than that by endocytosis labeling. Such a high labeling efficiency not only enables the ultrasensitive magnetic resonance imaging (MRI) detection of sub-10 cells and long-term tracking of transplanted MSCs over 10 weeks but also endows transplanted MSCs with a magnetic manipulation ability in vivo. A proof-of-concept study using a rat stroke model showed that the labeled MSCs facilitated MRI tracking and magnetic targeting for efficient replacement therapy with a significantly reduced dosage of 5 × 104 transplanted cells. The findings in this study have demonstrated the great potential of the magnetothermal approach as an efficient labeling technique for future clinical usage.

Ferromagnetic Vortex Iron Oxide Nanorings Modified with Integrin β1 Antibody for Targeted MRI Tracking of Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have demonstrated great potential for tissue engineering and regenerative medicine applications. Noninvasive and real-term tracking of transplanted MSCs in vivo is crucial for studying the distribution and migration of MSCs, and their role in tissue injury repair. This study reports on the use of ferrimagnetic vortex iron oxide (FVIO) nanorings modified with anti-human integrin β1 for specific recognition and magnetic resonance imaging (MRI) tracking of human MSCs (hMSCs). Integrin β1 is highly expressed at all stem cell proliferation and differentiation stages. Therefore, the anti-integrin β1 antibody (Ab) introduced in FVIO targets integrin β1, thus enabling FVIO to target stem cells at any stage. This is unlike the traditional MRI-based monitoring of transplanted stem cells, which usually requires pre-labeling the stem cells with tracers before injection. Because of the ability to recognize hMSCs, the Ab-modified FVIO nanotracers (FVIO-Ab) have the advantage of not requiring pre-labeling before stem cell transplantation. Furthermore, the FVIO-Ab nanotracers have high T*₂ contrast resulting from the unique magnetic properties of FVIO which can improve the MRI tracking efficiency of stem cells. This work may provide a new way for stem cell labeling and in vivo MRI tracking, thus reducing the risks associated with stem cell transplantation and promoting clinical translation.

In vivo MRI tracking and therapeutic efficacy of transplanted mesenchymal stem cells labeled with ferrimagnetic vortex iron oxide nanorings for liver fibrosis repair.

Mesenchymal stem cells (MSCs) have showed promising effects in the treatment of liver fibrosis. Long-term and noninvasive in vivo tracking of transplanted MSCs is essential for understanding the therapeutic mechanism of MSCs during the therapy of liver fibrosis. In this study, we report the development of a ferrimagnetic vortex iron oxide nanoring (FVIO)-based nanotracer for the long-term visualization of transplanted human MSCs (hMSCs) by magnetic resonance imaging (MRI). The FVIOs were prepared by a hydrothermal reaction followed by hydrogen reduction. To endow the FVIOs with biocompatibility, polyethylene glycol amine (mPEG-NH2) was covalently coupled on the surface of FVIOs, forming FVIO@PEG nanotracers with high contrast enhancement and intracellular uptake. The hMSCs labeled with FVIO@PEG nanotracers exhibited enhanced MRI contrast than those labeled with a commercial contrast agent, and could be continuously monitored by MRI in liver fibrosis mice for 28 days after transplantation, clearly clarifying the migration behavior of hMSCs in vivo. Moreover, we explored the therapeutic mechanism of the FVIO@PEG labeled hMSCs in the amelioration of liver fibrosis, including the reduction in inflammation and oxidative stress, the inhibition of hepatic fibrosis-caused histopathological damage, as well as the down-regulation of the expression of relevant cytokines. The results obtained in this work may deepen our understanding of the behavior and role of hMSCs in the treatment of liver fibrosis, which is key to the clinical application of stem cells in the therapy of liver diseases.

Precise Regulation of Enzyme-Nanozyme Cascade Reaction Kinetics by Magnetic Actuation toward Efficient Tumor Therapy.

Spatiotemporal regulation of multi-enzyme catalysis with stimuli is crucial in nature to meet different metabolic requirements but presents a challenge in artificial cascade systems. Here, we report a strategy for precise and tunable modulation of enzyme-nanozyme cascade reaction kinetics by remote magnetic stimulation. As a proof of concept, glucose oxidase (GOx) was immobilized onto a ferrimagnetic vortex iron oxide nanoring (Fe3O4 NR) functionalized with poly(ethylene glycol) of different molecular weights to construct a series of Fe3O4 NR@GOx with nanometer linking distances. The activities of GOx and the Fe3O4 NR nanozyme in these systems were shown to be differentially stimulated by Fe3O4 NR-mediated local heat in response to an alternating magnetic field (AMF), leading to modulated cascade reaction kinetics in a distance-dependent manner. Compared to the free GOx and Fe3O4 NR mixture, Fe3O4 NR(D2)@GOx with an optimum linking distance of 1 nm exhibits a superior kinetic match between GOx and the Fe3O4 NR nanozyme and over a 400-fold higher cascade activity under AMF exposure. This enables remarkable intracellular reactive oxygen species production and significantly improved tumor inhibition of AMF-stimulated Fe3O4 NR(D2)@GOx in 4T1 tumor-bearing mice. The strategy reported here offers a straightforward new tool for fine-tuning multi-enzyme catalysis at the molecular level using magnetic stimuli and holds great promise for use in a variety of biotechnology and synthetic biology applications.

Enabling contactless rapid on-demand debonding and rebonding using hysteresis heating of ferrimagnetic nanoparticles

Rapid and contactless on-demand debonding and rebonding of high-strength joints is a promising solution for quick attachment, repairs, disassembly, and recycling of structural systems. Herein we show that rapid and contactless on-demand debonding and rebonding can be achieved by incorporating ferrimagnetic iron oxide nanoparticles (Fe3O4) into poly(ethylene-methacrylic acid) (EMAA). When subjected to an external alternating magnetic field, the ferrimagnetic nanoparticles generate localized heat which melt the EMMAA, resulting in quick (<1 min) debonding and rebonding. The strength of the adhesive bond matches that achieved by conventional oven heating, exceeding the highest value reported for reversible adhesives in the literature. The results also show that, for the first time, the ferrimagnetic nanoparticles are effective in retaining 100% of the original bond strength for up to five cycles of repeated debonding and rebonding. Analytical and computational models have been developed to characterize the effects of key design parameters, such as Fe3O4 mass loading and magnetic flux on the heating performance and bond strength. The model correlates well with experimental results and reveals that magnetic hysteresis loss is more efficient than eddy current generated by conductive fillers for heating the adhesive. The high-strength EMAA/Fe3O4 adhesive is a very promising solution for contactless, on-demand, repeated adhesion applications to complex geometries and in hard-to-access locations.