Bare Superparamagnetic Iron Oxide Nanoparticles Research Articles

Stabilized Bare Superparamagnetic Iron Oxide Nanoparticles: Synthesis and Characterization

Iron is a ubiquitous element found on Earth's crust, existing in various forms, such as Magnetite (Fe3O4) and Hematite (α-Fe2O3). Magnetic iron oxide nanoparticles (MIONPs) have become increasingly popular because they possess unique properties such as high surface area to volume ratio, super-paramagnetic properties, photocatalytic properties, and economical synthesis methods. This study produced MIONPs using the co-precipitation method, stabilized by a molybdenum magnet. Two soluble iron salts (FeCl3.6H2O and FeSO4.7H2O) were reacted with 5N NH4OH solution at 80 °C in a nitrogen atmosphere. The MIONPs had a high saturation magnetization of 74.2emu/g, good crystallinity with crystalline spinel structured magnetite phase of iron oxide, high thermal stability depicted by 2.09 wt. % weight loss, and small particle sizes (6-25 nm). FTIR revealed a high-intensity peak at 546.28 cm-1, attributed to the Fe-O stretching bond. Furthermore, the study showed that the co-precipitation method could be used to produce nanoparticles with a wide range of properties that could be used for various applications. It is a promising solution for producing stabilized magnetic nanoparticles since it uses non-toxic reagents and a straightforward, secure technique. Therefore, it may be used to synthesize nanoparticles for targeted treatment, magnetic resonance imaging, drug delivery, water treatment purposes and environmental remediation.

Proteomic Analysis Reveals Distinct Protein Corona Compositions of Citrate- and Riboflavin-Coated SPIONs.

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as one of the most beneficial tools for biomedicine, especially in theranostic applications. Even though SPIONs have excellent properties regarding their biocompatibility and unique magnetic properties, they lack stability in biological fluids. To stabilize and increase the specificity of the SPIONs to target desirable cells or tissues, several surface coatings have been introduced. These surface coatings can lead to different preferences of serum protein bindings, which ultimately determine their behaviors in vitro and in vivo. Thus, understanding the interaction of SPIONs with biological systems is important for their biocompatible design and clinical applications. In this study, using proteomic analyses, we analyzed the protein corona fingerprints on SPIONs with two different coatings, including citrate and riboflavin, that have been widely used as surface coatings and ligands for enhancing cellular uptake in breast cancer cells. Though both citrate-coated SPIONs (C-SPIONs) and riboflavin-coated SPIONs (Rf-SPIONs) showed similar sizes and zeta potentials, we found that Rf-SPIONs adsorbed more serum proteins than bare SPIONs (B-SPIONs) or C-SPIONs, which was likely due to the higher hydrophobicity of the riboflavin. The enriched proteins consisted mainly of immune-responsive and blood coagulation proteins with different fingerprint profiles. Cellular uptake studies in MCF-7 breast cancer cells comparing the activities of preformed and in situ coronas showed different uptake behaviors, suggesting the role of protein corona formation in promoting the interaction between the SPIONs and the cells. The results obtained here provide the essential information for further development of the potential strategy to reduce or stimulate immune response in vivo to increase therapeutic applications of both C-SPIONs and Rf-SPIONs.

Curing epoxy with polyvinylpyrrolidone (PVP) surface-functionalized NixFe3-xO4 magnetic nanoparticles

Cathodic electrodeposition method was applied in synthesis of three types of superparamagnetic iron oxide nanoparticles (SPIONs): bare SPIONs, polyvinylpyrrolidone (PVP)-coated SPIONs (PVP-SPIONs) and Ni2+-doped PVP-SPIONs (PVP/Ni-SPIONs). The synthesized nanoparticles were well characterized by X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FE-SEM), and vibrating sample magnetometer (VSM). The potential of the modified SPIONs for curing in an epoxy/amine system having very low nanoparticle concentration was investigated in terms of Cure Index applying nonisothermal differential scanning calorimetry (DSC) at different heating rates. A shift in cure behavior from Poor to Good crosslinked epoxy networks by replacing PVP-SPIONs by PVP/Ni-SPIONs in the system was indicative of complementary role of SPIONs doping in Ni, which improved activation of surafce SPIONs towards PVP macromolecule, then thanks to its catalyzing effect enhanced epoxy ring opening due to Ni2+ cations incorporation.

Inhibitive effect of super paramagnetic iron oxide nanoparticles on the alkaline hydrolysis of procaine

The Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) can bind drugs and act as drug-carriers. The magnetically active SPIONs can be used to deliver the drugs to the target through magnetic fields. The objective of the present work has been undertaken to study the stability, and binding behaviour of procaine with SPIONs and surfactant-coated SPIONs. Procaine is among the ester drugs and hydrolyses in the alkaline medium. The influence of SPIONs and surfactant-coated SPIONs on the rate of hydrolysis of procaine in alkaline medium may help to define the behaviour of the drug in the presence of these nanoparticles. The kinetic studies of procaine hydrolysis in the presence of SPIONs and surfactant-coated SPIONs were carried out spectrophotometrically. The concentrations of OH− ions were taken in excess over [procaine] to keep the reaction conditions under pseudo-first-order. The presence of SPIONs and the SPIONs coated with cetyltrimethylammonium bromide; CTABr and sodium dodecylsulphate; SDS surfactants displayed an inhibitive effect on the rate of hydrolysis of procaine. The synthesised nanoparticles were characterised using X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The kψ-[surfactant] profile in the presence of SPIONs was discussed using the pseudophase model in which the reactants are considered to be distributed in the aqueous and micellar media. The rate constant for the procaine hydrolysis and the binding constants of procaine with coated and non-coated SPIONs have been calculated by analysing the data for the variation in the rate constant with the change in [surfactant], [SPIONs] and [surfactant-coated SPIONs].Graphic abstractThe studies on the rate of hydrolysis of procaine in the presence of SPIONs and surfactant-coated SPIONs shows inhibitive effects of NPs on the reaction. Procaine has good binding affinity with surfactant-coated SPIONs in comparison with the bare SPIONs.

Interaction of superparamagnetic iron oxide nanoparticles with DNA and BSA

Background: Superparamagnetic iron oxide nanoparticles (SPION) are widely used in various biomedical technologies, in particular, as carriers for drug delivery to the target. Since SPION-drug complexes are planned to be used in vivo, it is necessary to find out if competitive binding of nanoparticles with biologically important macromolecules (nucleic acids and proteins) is possible. Objectives: To investigate the possibility of complexation of iron oxide nanoparticles with DNA and serum albumin. Materials and methods: Bare and sodium citrate coated SPION with different surface charges, bovine serum albumin (BSA) and calf thymus DNA were used. The complexes of SPION and macromolecules were precipitated by an external magnetic field. The research was carried out by spectrophotometry in visible and ultraviolet ranges. Results: To study SPION interactions with DNA and BSA, the spectra of supernatants of the binary systems were compared with the spectra of the corresponding control macromolecules solutions. In the DNA-SPION systems, a decrease in the DNA absorption is observed only for bare nanoparticles. Our estimation shows that the maximum possible concentration ratio of bound DNA to SPION is about 2.5×10-4 mol/g. The addition of sodium citrate coated SPION to the DNA solution does not cause any spectral changes of the supernatant. The interaction of BSA with SPION, coated with sodium citrate, leads to a slight increase in supernatant absorption compared with the one of the control protein solution. It can be caused by the fact that the resulting complexes are not precipitated by a magnetic field. No difference between the spectrum of the supernatant of BSA-bare SPION system and the control protein solution was observed. Conclusions: The obtained spectrophotometric results demonstrate the formation of complexes between DNA and bare iron oxide nanoparticles as well as between BSA and the nanoparticles, coated with sodium citrate. The maximum concentration ratio of bound DNA and bare SPION was obtained for the investigated system. It is necessary to take into account when SPION are used as carriers for drug delivery.

Triple Therapy of HER2+ Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.

By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2+ cells and tumor (HER2+)-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) 111In-labeled, antibody-conjugated surface-modified SPIONs; and (4) 111In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

Receptor-Meditated Endocytosis by Hyaluronic Acid@Superparamagnetic Nanovetor for Targeting of CD44-Overexpressing Tumor Cells.

The present report proposes a more rational hyaluronic acid (HA) conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs) by covalently binding the targeting molecules (HA) with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA)@SPIONs was included oxidization of nanoparticle’s surface with H2O2 followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells. Fourier transform infrared (FTIR) and zeta-potential studies confirmed the chemical bonding between amino acid linker and polysaccharides. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed that HA-SPIONs-treated cells remained 82.9% ± 2.7% alive at high particle dosage (200 µg/mL iron concentration), whereas GA-SPIONs and bare SPIONs (B-SPIONs) treated cells had only 59.3% ± 13.4% and 26.5% ± 3.1% survival rate at the same conditions, respectively. Confocal microscopy analysis showed increased cellular internalization of HA-SPIONs compared to non-interacting agarose coated SPIONs (AgA-SPIONs).

PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have enticed attention on the grounds of their unique physicochemical properties as well as potential applications in magnetic hyperthermia, immunoassays, as a contrast agent in magnetic resonance imaging and targeted drug delivery among others. Toward this goal, we synthesized SPIONs by chemical co-precipitation and PEGylated it. PEGylated SPIONs (PS) were studied for its detailed in vivo toxicity profile, in view of further surface engineering for its clinical applications. The intravenous LD50(14) of the PS was ascertained as 508.16 ± 41.52 mg/kg b wt. Histopathology of the vital organs of the animals injected with acute toxic doses showed pathological changes in spleen, lung, liver, and kidney. Accumulation of SPION was found in the aforementioned organs as confirmed by Prussian blue staining. Further, 1/10th dose of LD50(14) of PS and the Bare SPION (BS) was used to analyze a detailed toxicity profile, including genotoxicity (micronuclei formation and chromosomal aberration assays), organ-specific toxicity (a detailed serum biochemical analysis), and also determination of oxidative stress. The results of toxicity profile indicated no significant toxicity due to systemic exposure of PS. Atomic absorption spectroscopy (AAS) analysis confirmed the accumulation of SPION majorly in lungs, liver spleen, and kidneys. The present study thus indicated an optimal dose of PS which could be used for surface modification for targeted drug delivery applications with least toxicity.

Functionalization of strongly interacting magnetic nanocubes with (thermo)responsive coating and their application in hyperthermia and heat-triggered drug delivery.

Herein, we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermoresponsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR), but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermoresponsive shell is composed of poly(N-isopropylacrylamide-co-polyethylene glycolmethyl ether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.

SPION-mediated soil DNA extraction and comparative analysis with conventional and commercial kit-based protocol

Direct isolation of soil DNA comes as an emerging technology to understand the microbial diversity of a particular environment circumventing the dependency on culturable methods. Soil DNA isolation is tough due to the presence of various organic components present in soil which interfere in extraction procedure. Here, we report a novel direct soil DNA extraction protocol utilizing bare superparamagnetic iron oxide nanoparticles and its comparison with conventional and commercial kit-based soil DNA extraction methods. The quality, quantity and feasibility of the recovered DNA from all the three methods towards various molecular techniques were checked. Our magnetic nanoparticle-based soil DNA extraction successfully yields pure DNA without any RNA or protein contamination as revealed by the nanodrop spectrophotometer and agarose gel electrophoretic study. Different methods of soil DNA extraction were evaluated on the basis of PCR, denaturing gradient gel electrophoresis and real-time PCR. Soil DNA extracted using conventional method fails to carry out critical molecular biology techniques where as magnetic nanoparticle-based soil DNA extraction gave good results which is comparable to commercial kit. This comparative study suggests that protocol described in this report is novel, less time consuming, cost effective with fewer handling steps and yields high quantity, good quality DNA from soil.

Interaction of bare and gold-coated superparamagnetic iron oxide nanoparticles with fetal bovine serum

Superparamagnetic iron oxide nanoparticles (SPIONs) are being increasingly used in various biomedical processes such as hyperthermia, cell and protein separation, enhancing resolution of magnetic resonance imaging and drug delivery. Here, SPIONs were prepared by optimized co-precipitation of iron chlorides in basic medium and then coated with gold. Bare SPIONs and Aucoated SPIONs were characterized by TEM before incubation with fetal bovine serum for 0.5, 1, 2, 4, 8 and 24 h. After these interaction times, the mixture was deposed on a small column in a strong magnetic field (MACS®system). The SPIONs were retained; different washing fractions were collected and studied by UV-Vis spectroscopy and by 1D gel electrophoresis. The study revealed the presence of proteins in the washing solutions and confirmed the strong interaction of the protein with the SPIONs.

Toxicity Evaluations of Superparamagnetic Iron Oxide Nanoparticles: Cell “Vision” versus Physicochemical Properties of Nanoparticles

In the last few decades, nanoparticles (NPs) have been recognized as promising candidates for starting a new revolution in science and technology due to their unusual properties, attracting the attention of physicists, chemists, biologists, and engineers. The aim of this study is to evaluate the toxicities (at both cellular and molecular levels) of three forms of superparamagnetic iron oxide nanoparticles (SPIONs) of various surface chemistries (COOH, plain, and NH(2)) through the comparison with gene expression patterns of three cell types (i.e., human heart, brain, and kidney). For this purpose, both an MTT assay and a DNA microarray analysis were applied in three human cell lines--HCM (heart), BE-2-C (brain), and 293T (kidney)--under the exposure to SPIONs-COOH, SPIONs-NH(2), and bare SPIONs. The specific gene alteration and hierarchical clustering revealed that SPIONs-COOH altered genes associated with cell proliferative responses due to their reactive oxygen species (ROS) properties. It was also found that the cell type can have quite a significant role in the definition of suitable pathways for detoxification of NPs, which has deep implications for the safe and high yield design of NPs for biomedical applications and will require serious consideration in the future.

Hyaluronidase-sensitive SPIONs for MR/optical dual imaging nanoprobes

This study developed new enzyme-specific superparamagnetic iron oxide nanoparticles (SPIONs) with potential as a multimodal probe in magnetic resonance (MR) imaging and optical imaging. For the MR/optical dual imaging, SPIONs were coated with near-infrared fluorescence dye (Cy5.5)-labeled hyaluronic acid (Cy5.5-HA), which could be readily degraded by hyaluronidase (HAdase). The presence of HA on the coated SPION was confirmed using FTIR, X-ray diffraction, and thermogravimetric analysis. Physicochemical analyses of Cy5.5-HA-coated SPIONs (Cy5.5-HA-SPIONs) demonstrated their higher colloidal stability and T2 relaxivity than bare SPIONs. When Cy5.5-HA-SPIONs were exposed to the MR instrument for the phantom test, the dark intensity of their T2-weighted image increased in a Fe concentration-dependent manner, suggesting potential as the MR probe. To examine their ability as the enzyme-sensitive optical probe, the fluorescent signals of Cy5.5-HA-SPIONs were measured in the absence or presence of HAdase. In the absence of HAdase, Cy5.5-HA-SPIONs showed a negligible fluorescent signal due to possible quenching between a SPION and fluorescence dye, and self-quenching effect of Cy5.5 molecules. On the other hand, in the presence of HAdase, the fluorescent signal of Cy5.5-HA-SPIONs increased dramatically as a function of the HAdase concentration, resulting from the degradation of the HA backbone. These results suggest that the Cy5.5-HA-SPION is useful as a multimodal nanoprobe for MR imaging and HAdase-sensitive optical imaging.