Ultrasmall Superparamagnetic Iron Oxide Nanoparticles Research Articles

Preliminary Findings on the Effect of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles and Acute Stress on Selected Markers of Oxidative Stress in Normotensive and Hypertensive Rats.

Several studies have reported that the administration of various nanoparticles in vivo can cause oxidative stress. The combination of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) and acute stress was selected because, during intravenous application of a contrast agent, patients are exposed to psycho-emotional stress. This study was designed to investigate the effect of acute stress and USPIONs on selected markers of oxidative stress (antioxidant capacity, superoxide dismutase, glutathione peroxidase and catalase activities, levels of advanced oxidation protein products, protein carbonyls, lipoperoxides and 8-isoprostanes) in plasma and erythrocytes in normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the WKY and SHR groups, there was a significant main effect of genotype between groups on studied markers except protein carbonyls and lipoperoxides. In SHR, the combination of acute stress and USPIONs increased the antioxidant capacity of plasma and the selected enzyme activities of erythrocytes. In WKY, the combination of acute stress and USPIONs decreased the antioxidant capacity of erythrocytes and reduced levels of advanced oxidation protein products in plasma. Our study points to the fact that, when hypertensive subjects are treated with iron oxide nanoparticles, caution should be taken, especially in stress conditions, since they seem to be more vulnerable to oxidative stress produced by USPIONs.

Extracellular Vesicle-Mediated Delivery of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles to Mice Brain.

Extracellular vesicles (EVs) are small lipid membrane-bound vesicles that can pass the blood–brain barrier. Therefore, EVs could be used for the delivery of therapeutics to the brain. Herein, we investigated the biodistribution of intranasal perfusion of ultrasmall superparamagnetic iron oxide (USPIO)-labeled astrocyte-derived EVs (ADEVs) in mice. We used Western blotting, transmission electron microscopy (TEM), and nanoparticle uptake assay to characterize ADEVs. In addition, intranasal perfusion coupled with magnetic resonance imaging (MRI) was employed to determine the distribution of USPIO-labeled ADEVs in mice. Our results showed the uptake of USPIO by mouse astrocytes and ADEVs. In addition, we confirmed the biodistribution of ADEVs in the brain and other internal organs, including the kidneys, liver, and spleen. Our results suggest that USPIO did not affect mouse astrocyte cell survivability and EV release. Therefore, intranasal delivery of therapeutic loaded EVs could be used for the treatment of various brain disorders.

Ultrasmall Superparamagnetic Iron Oxide Nanoparticles Synthesized by Micellar Approach as a Potential Dual-Mode T1-T2 Contrast Agent

Purpose: A micellar approach is used to synthesize Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs) with an average diameter of 3.4±0.5 nm, suitable for dual-mode T1-T2 contrast agents. Methods: Micelles with 3.8 nm, measured by dynamic light scattering, were obtained by self-organizing the surfactant iron(III) dodecyl sulfate (IDS) in 1-octanol. IDS was prepared by replac-ing Na+ cation in sodium dodecyl sulfate molecule, and its critical micelle concentration (CMC) was measured by electrical conductivity. The USPIONs were synthesized in a biphasic system: IDS in octanol (55% above the CMC) and water containing NaBH4. Results: A yellow precipitate is immediately formed at the water/alcohol interface, rapidly changes to a black one, and transfers to the aqueous phase. The magnetite phase was confirmed by X-ray diffraction and Mössbauer spectroscopy. The magnetic behavior shows a major paramagnetic char-acter with a weak ferromagnetic component at 5 K, the latter attributed to the interparticle couplings below its blocking temperature (TB = 35 K). The particles were coated with carboxymethyl dextran, showing an isoelectric point of 2.7 with electrokinetic potential around -30 mV in the physiological pH range. Magnetic relaxation measurements showed relaxivity values r1 = 0.17 mM-1 s-1 and r2 = 1.73 mM-1 s-1 (r2/r1 = 10) in a 3T field. These values infer that the ultrasmall size affects the interac-tions with the protons of the nearby water molecules. The r2 value decreases because the core mag-netization decreases with size; r1 intensifies due to the high surface. Conclusion: The results show a system with high colloidal stability, non-cytotoxic, and potential application as T1-T2 dual-mode contrast agents.

Towards Clinical Translation of Melt Electrowritten Scaffolds: Visualisation of USPIO Labelled Polycaprolactone Scaffolds by Magnetic Resonance Imaging

Objective: Melt electrowriting (MEW) is an advanced fibre forming technology for 3D printing of complex scaffold architectures, which have convincingly shown their potential in cardiovascular constructs.1,2 Driven by electrohydrodynamic forces, a polymer fibre jet is digitally controlled to form microfibrous scaffolds via a direct writing approach. Clinical translation of such grafts requires establishing monitoring options, such as with magnetic resonance imaging (MRI). Consequently, this work proposes the labelling of medical grade polycaprolactone (PCL) with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles as contrast agents to render the melt electrowritten composite scaffolds detectable via MRI.

Magnetic Ordering in Ultrasmall Potassium Ferrite Nanoparticles Grown on Graphene Nanoflakes.

Magnetic nanoparticles are central to the development of efficient hyperthermia treatments, magnetic drug carriers, and multimodal contrast agents. While the magnetic properties of small crystalline iron oxide nanoparticles are well understood, the superparamagnetic size limit constitutes a significant barrier for further size reduction. Iron (oxy)hydroxide phases, albeit very common in the natural world, are far less studied, generally due to their poor crystallinity. Templating ultrasmall nanoparticles on substrates such as graphene is a promising method to prevent aggregation, typically an issue for both material characterization and applications. We generate ultrasmall nanoparticles, directly on the carbon framework by the reaction of a graphenide potassium solution, charged graphene flakes, with iron(II) salts. After mild water oxidation, the obtained composite material consists of ultrasmall potassium ferrite nanoparticles bound to the graphene nanoflakes. Magnetic properties as evidenced by magnetometry and X-ray magnetic circular dichroism, with open magnetic hysteresis loops near room temperature, are widely different from classical ultrasmall superparamagnetic iron oxide nanoparticles. The large value obtained for the effective magnetic anisotropy energy density Keff accounts for the presence of magnetic ordering at rather high temperatures. The synthesis of ultrasmall potassium ferrite nanoparticles under such mild conditions is remarkable given the harsh conditions used for the classical syntheses of bulk potassium ferrites. Moreover, the potassium incorporation in the crystal lattice occurs in the presence of potassium cations under mild conditions. A transfer of this method to related reactions would be of great interest, which underlines the synthetic value of this study. These findings also give another view on the previously reported electrocatalytic properties of these nanocomposite materials, especially for the sought-after oxygen reduction/evolution reaction. Finally, their longitudinal and transverse proton NMR relaxivities when dispersed in water were assessed at 37 °C under a magnetic field of 1.41 T, allowing potential applications in biological imaging.

Janus USPION modular platform (JUMP) for theranostic ultrasound-mediated targeted intratumoral microvascular imaging and DNA/miRNA delivery.

Rationale: High mortality in pancreatic cancer (PDAC) and triple negative breast cancer (TNBC) highlight the need to capitalize on nanoscale-design advantages for multifunctional diagnostics and therapies. DNA/RNA-therapies can provide potential breakthroughs, however, to date, there is no FDA-approved systemic delivery system to solid tumors. Methods: Here, we report a Janus-nanoparticle (jNP)-system with modular targeting, payload-delivery, and targeted-imaging capabilities. Our jNP-system consists of 10 nm ultrasmall superparamagnetic iron oxide nanoparticles (USPION) with opposing antibody-targeting and DNA/RNA payload-protecting faces, directionally self-assembled with commercially available zwitterionic microbubbles (MBs) and DNA/RNA payloads. Results: Sonoporation of targeted jNP-payload-MBs delivers functional reporter-DNA imparting tumor-fluorescence, and micro-RNA126 reducing non-druggable KRAS in PDAC-Panc1 and TNBC-MB231 xenografted tumors. The targeting jNP-system enhances ultrasound-imaging of intra-tumoral microvasculature using less MBs/body weight (BW). The jNP-design enhances USPION's T2*-magnetic resonance (MR) and MR-imaging of PDAC-peritoneal metastases using less Fe/BW. Conclusion: Altogether, data advance the asymmetric jNP-design as a potential theranostic Janus-USPION Modular Platform - a JUMP forward.

Engineered Protein-Iron Oxide Hybrid Biomaterial for MRI-traceable Drug Encapsulation.

Labeled protein-based biomaterials have become a popular for various biomedical applications such as tissue-engineered, therapeutic, or diagnostic scaffolds. Labeling of protein biomaterials, including with ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging techniques. These USPIO-based biomaterials are widely studied in magnetic resonance imaging (MRI), thermotherapy, and magnetically-driven drug delivery which provide a method for direct and non-invasive monitoring of implants or drug delivery agents. Where most developments have been made using polymers or collagen hydrogels, shown here is the use of a rationally designed protein as the building block for a meso-scale fiber. While USPIOs have been chemically conjugated to antibodies, glycoproteins, and tissue-engineered scaffolds for targeting or improved biocompatibility and stability, these constructs have predominantly served as diagnostic agents and often involve harsh conditions for USPIO synthesis. Here, we present an engineered protein-iron oxide hybrid material comprised of an azide-functionalized coiled-coil protein with small molecule binding capacity conjugated via bioorthogonal azide-alkyne cycloaddition to an alkyne-bearing iron oxide templating peptide, CMms6, for USPIO biomineralization under mild conditions. The coiled-coil protein, dubbed Q, has been previously shown to form nanofibers and, upon small molecule binding, further assembles into mesofibers via encapsulation and aggregation. The resulting hybrid material is capable of doxorubicin encapsulation as well as sensitive T2*-weighted MRI darkening for strong imaging capability that is uniquely derived from a coiled-coil protein.

Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex.

Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion.Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP).Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP.Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization.

Microemulsion-Confined Biomineralization of PEGylated Ultrasmall Fe3O4 Nanocrystals for T2-T1 Switchable MRI of Tumors.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are a novel T1 contrast agent with good biocompatibility and switchable imaging signal that have not been widely applied for magnetic resonance imaging (MRI) because it is difficult to induce their relatively close ideal agglomeration. Here, by combining the microemulsion method with the biomineralization principle, a pH-responsive T2-T1 switchable MRI nanoprobe was constructed via the microemulsion-confined biomineralization of PEGylated USPIONs (PEG-USPIONs). The size of the formed CaCO3-coated PEG-USPION conjugates (PEG-USPIONs@CaCO3 nanoprobe) was uniform and controllable, and the preparation method was simple. The PEG-USPIONs inside the nanoconjugates agglomerate more tightly, and the T1-MRI signal of the nanoprobe is converted to the T2-MRI signal. When exposed to the acidic environment of the tumor tissue or internal organelles, the CaCO3-coating of the nanoprobes is dissolved, and free PEG-USPIONs are released, thus realizing the T1-weighted imaging of the tumors. The suitability of the PEG-USPIONs@CaCO3 nanoprobe for tumor MRI detection was successfully demonstrated using a mouse model bearing a subcutaneous 4T1 xenograft.

Ultrasmall superparamagnetic iron oxide nanoparticles: A next generation contrast agent for magnetic resonance imaging.

As a research hotspot, the development of magnetic resonance imaging (MRI) contrast agents has attracted great attention over the past decades for improving the accuracy of diagnosis. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with core diameter smaller than 5.0nm are expected to become a next generation of contrast agents owing to their excellent MRI performance, long blood circulation time upon proper surface modification, renal clearance capacity, and remarkable biosafety profile. On top of these merits, USPIO nanoparticles are used for developing not only T1 contrast agents, but also T2 /T1 switchable contrast agents via assembly/disassembly approaches. In recent years, as a new type of contrast agents, USPIO nanoparticles have shown considerable applications in the diagnosis of various diseases such as vascular pathological changes and inflammations apart from malignant tumors. In this review, we are focusing on the state-of-the-art developments and the latest applications of USPIO nanoparticles as MRI contrast agents to discuss their advantages and future prospects. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Citrate-Coated Magnetic Polyethyleneimine Composites for Plasmid DNA Delivery into Glioblastoma

Several ternary composites that are based on branched polyethyleneimine (bPEI 25 kDa, polydispersity 2.5, 0.1 or 0.2 ng), citrate-coated ultrasmall superparamagnetic iron oxide nanoparticles (citrate-NPs, 8–10 nm, 0.1, 1.0, or 2.5 µg), and reporter circular plasmid DNA pEGFP-C1 or pRL-CMV (pDNA 0.5 µg) were studied for optimization of the best composite for transfection into glioblastoma U87MG or U138MG cells. The efficiency in terms of citrate-NP and plasmid DNA gene delivery with the ternary composites could be altered by tuning the bPEI/citrate-NP ratios in the polymer composites, which were characterized by Prussian blue staining, in vitro magnetic resonance imaging as well as green fluorescence protein and luciferase expression. Among the composites prepared, 0.2 ng bPEI/0.5 μg pDNA/1.0 µg citrate-NP ternary composite possessed the best cellular uptake efficiency. Composite comprising 0.1 ng bPEI/0.5 μg pDNA/0.1 μg citrate-NP gave the optimal efficiency for the cellular uptake of the two plasmid DNAs to the nucleus. The best working bPEI concentration range should not exceed 0.2 ng/well to achieve a relatively low cytotoxicity.

Integrin \u03b1v\u03b26-targeted MR molecular imaging of breast cancer in a xenograft mouse model

BackgroundThe motif RXDLXXL-based nanoprobes allow specific imaging of integrin αvβ6, a protein overexpressed during tumorigenesis and tumor progression of various tumors. We applied a novel RXDLXXL-coupled cyclic arginine-glycine-aspartate (RGD) nonapeptide conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (referred to as cFK-9-USPIO) for the application of integrin αvβ6-targeted magnetic resonance (MR) molecular imaging for breast cancer.MethodsA novel MR-targeted nanoprobe, cFK-9-USPIO, was synthesized by conjugating integrin αvβ6-targeted peptide cFK-9 to N-amino (−NH2)-modified USPIO nanoparticles via a dehydration esterification reaction. Integrin αvβ6-positive mouse breast cancer (4 T1) and integrin αvβ6 negative human embryonic kidney 293 (HEK293) cell lines were incubated with cFK-9-AbFlour 647 (blocking group) or cFK-9-USPIO (experimental group), and subsequently imaged using laser scanning confocal microscopy (LSCM) and 3.0 Tesla magnetic resonance imaging (MRI) system. The affinity of cFK-9 targeting αvβ6 was analyzed by calculating the mean fluorescent intensity in cells, and the nanoparticle targeting effect was measured by the reduction of T2 values in an in vitro MRI. The in vivo MRI capability of cFK-9-USPIO was investigated in 4 T1 xenograft mouse models. Binding of the targeted nanoparticles to αvβ6-positive 4 T1 tumors was determined by ex vivo histopathology.ResultsIn vitro laser scanning confocal microscopy (LSCM) imaging showed that the difference in fluorescence intensity between the targeting and blocking groups of 4 T1 cells was significantly greater than that in HEK293 cells (P < 0.05). The in vitro MRI demonstrated a more remarkable T2 reduction in 4 T1 cells than in HEK293 cells (P < 0.001). The in vivo MRI of 4 T1 xenograft tumor-bearing nude mice showed significant T2 reduction in tumors compared to controls. Prussian blue staining further confirmed that αvβ6 integrin-targeted nanoparticles were specifically accumulated in 4 T1 tumors and notably fewer nanoparticles were detected in 4 T1 tumors of mice injected with control USPIO and HEK293 tumors of mice administered cFK-9-USPIO.ConclusionsIntegrin αvβ6-targeted nanoparticles have great potential for use in the detection of αvβ6-overexpressed breast cancer with MR molecular imaging.

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats.

We determined erythrocyte physiological and biochemical properties after the single and repeated administration of ultra-small superparamagnetic iron-oxide nanoparticles (USPIONs) in normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Polyethylene glycol-coated USPIONs (transmission electron microscope detected a mean size of ~30 nm and hydrodynamic size ~51 nm) were intravenously administered to rats either in one infusion at nominal dose 1 mg Fe/kg or in two infusions (administered with a difference of 24 h) at nominal dose 2 mg Fe/kg. Results showed that USPIONs did not deteriorate erythrocyte deformability, nitric oxide production, and osmotic resistance in both experimental settings. Both the single and repeated USPION administration elevated erythrocyte deformability in WKY. However, this effect was not present in SHR; deformability in USPION-treated SHR was significantly lower than in USPION-treated WKY. Nitric oxide production by erythrocytes was increased after a single USPION treatment in WKY, so it can be associated with improvement in erythrocyte deformability. Using biomagnetometry, we revealed significantly lower amounts of USPION-originated iron in erythrocytes in SHR compared with WKY. We found a much faster elimination of USPIONs from erythrocytes in hypertensive rats compared with the normotensive ones, which might be relevant for clinical practice in hypertensive patients undergoing clinical examination with the use of iron-oxide nanoparticles.

In vivo evaluation of toxicity and anti-inflammatory activity of iron oxide nanoparticles conjugated with ibuprofen.

Aim: The low solubility and consequent poor bioavailability of ibuprofen (IBU) is a major drawback that can be overcome by anchoring IBU on ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) as effective multifunctional carriers for drug delivery. Methods: USPIONs were conjugated with glycerol phosphate (USPION-GP) and also co-conjugated with IBU (USPION-GP/IBU), and their in vivo toxicity and anti-inflammatory effects investigated. Phosphate buffer saline (control), IBU, USPION-GP and USPION-GP/IBU were intravenously administered 15min before lipopolysaccharide-induced peritonitis in male Balb/c mice. Results: 4h later, USPION bioconjugates did not appear to have caused toxicity to blood leukocytes or caused alterations in the spleen, liver or kidneys. Also, they inhibited lipopolysaccharide-induced neutrophil mobilization into the peritoneum. Conclusion: The absence of systemic toxicity and the unexpected anti-inflammatory action of USPION bioconjugates indicates that they could be a novel and effective approach to administer IBU and warrant further investigation.

Magnetic Characterization and Moderate Cytotoxicity of Magnetic Mesoporous Silica Nanocomposite for Drug Delivery of Naproxen.

In this study, we describe the magnetic and structural properties and cytotoxicity of drug delivery composite (DDC) consisting of hexagonally ordered mesoporous silica, iron oxide magnetic nanoparticles (Fe2O3), and the drug naproxen (Napro). The nonsteroidal anti-inflammatory drug (NSAID) naproxen was adsorbed into the pores of MCM-41 silica after the ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) encapsulation. Our results confirm the suppression of the Brownian relaxation process caused by a “gripping effect” since the rotation of the whole particle encapsulated in the porous system of mesoporous silica was disabled. This behavior was observed for the first time, to the best of our knowledge. Therefore, the dominant relaxation mechanism in powder and liquid form is the Néel process when the rotation of the nanoparticle’s magnetic moment is responsible for the relaxation. The in vitro cytotoxicity tests were performed using human glioma U87 MG cells, and the moderate manifestation of cell death, although at high concentrations of studied systems, was observed with fluorescent labeling by AnnexinV/FITC. All our results indicate that the as-prepared MCM-41/Napro/Fe2O3 composite has a potential application as a drug nanocarrier for magnetic-targeted drug delivery.

A Magnetic T7 Peptide&AS1411 Aptamer-Modified Microemulsion for Triple Glioma-Targeted Delivery of Shikonin and Docetaxel.

Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe3O4@T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe3O4), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe3O4@T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe3O4@T7/AS1411/DTX&SKN-M encapsulated Fe3O4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG2000-T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe3O4@T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe3O4@T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe3O4@T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation

Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.

Assembly of USPIO/MOF nanoparticles with high proton relaxation rates for ultrasensitive magnetic resonance sensing

We develop a magnetic resonance sensor (MRS) based on the assembly of ultra-small superparamagnetic iron oxide (USPIO) nanoparticles and metal organic framework (MOF) materials, which have high T2 proton relaxation rates (r2).

Measurement of BAT activity by targeted molecular magnetic resonance imaging

ObjectiveThe aim of this study was to measure brown adipose tissue (BAT) activity by targeted peptide (CKGGRAKDC-NH2)-coupled, polyethylene glycol (PEG)-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with magnetic resonance imaging (MRI). MethodsThe peptide was conjugated with PEG-coated USPIO to obtain targeted probes. Male C57BL/6 J mice were randomly divided into cold exposing and control group (n = 5 per group). T2*-weighted images were obtained pre- and post-contrast probes. Histological and gene expression analyses were carried out. ResultsT2* relaxation time of BAT in the cold exposing group decreased more significantly compared to the control group. The calculated R2* increased with the reduction of T2* value. The ΔR2* (26.68 s−1) of BAT in the cold exposing group was significantly higher (P < 0.05) than the control group. Iron particle sediments in BAT of the cold exposing group were revealed more than the control group with Prussian blue staining. The UCP1 expression level was up-regulated after cold activation. ConclusionsBAT activity could be measured in vivo by the targeted peptide-coupled, PEG-coated USPIOs with MRI.

Citric acid coated ultrasmall superparamagnetic iron oxide nanoparticles conjugated with lactoferrin for targeted negative MR imaging of glioma.

The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of -7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.