Water-soluble Iron Oxide Nanoparticles Research Articles

SPIONs magnetic nanoparticles for MRI applications: Microwave synthesis and physicochemical, magnetic and biological characterizations

More and more biomedical applications used nanoparticles to improve their quality and their possibilities. Among the nanoparticles used, Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are often used because these nanoparticles are biocompatible, non-toxic and the ease of synthesizing them. The aim of this study is to obtain highly water-soluble iron oxide nanoparticles using a microwave process. The SPIONs developped with this technique have a diameter between 2 nm and 4 nm range, are monodisperse and stable in an aqueous media. Indeed, with the microwaves, the control of the temperature is more precise and allows so to obtain nanoparticles with a same diameter. After the synthesis, several characterizations are carried out to determine the shape, the size, the chemical composition, the stability and the magnetic properties. Then, these SPIONs can use to control the regeneration of tissues such as cartilage tissue. For that, SPIONs are internlasized in mesenchymal stromal cells (MSCs) because these cells can to differenciate into all humans cells and allows so to regenerate all tissues: these cells are good candidate for tissue engineering. In this work, the internalization of SPIONs and the cytotocixity are studied and confirm the biocompatibility of our SPIONs. Then, for the control of the regeneration of tissues, relaxometry and MRI (Magnetic Resonance Imaging) of SPIONs are realized to compare with the commercial contrast agent present (Endorem®). For our SPIONs, the values of transverse and longitudinal relaxivities are high and in the same order to Endorem®.

Efficient Synthesis of Water-Soluble Magnetic Nanoparticles and Its Application in MRI in the Detection of Intracranial Aneurysm

Magnetic nanoparticles were used in medical images, which could further improve image clarity, while watersoluble nanoparticles put forward more new requirements for the biocompatibility of nanoparticles. This research adopted a simple and novel method to prepare water-soluble iron oxide nanoparticles. First, transmission electron microscope (TEM) was used to analyze the size distribution of the prepared product; X-ray diffraction (XRD) was used to test the crystal structure of the prepared sample; the fast Fourier transform (FFT) spectrum was introduced to analyze the structural properties of the nanoparticles; the nanoparticle aqueous solutions of different concentrations were designed, and the impact of water-soluble nanoparticles on magnetic resonance imaging (MRI) was examined with the nuclear magnetic resonance spectrometer. At the same time, the prepared water-soluble nanoparticle solution was used for high-resolution tumor wall imaging of patients with unruptured intracranial aneurysm (IA) to compare the imaging effect of the aneurysm wall before and after the introduction of nanoparticles. In the material characterization test of nanoparticles, the prepared samples did not have certain iron oxide characteristic peaks, which means the synthesized iron oxide nanoparticles did not have a fixed crystal morphology. The samples tested by energy dispersive spectrometer (EDS) also contained Fe, O, C and Na. The average particle size was 5.8 nm. It was found under high-resolution TEM that the particle mirror spacing was 0.48 nm, which was consistent with the 111-crystal plane of Fe3O4; The magnetic hysteresis loop test confirmed that when the concentration of nanoparticles increased, the solution would form a magnetic fluid. When the concentration of aqueous solution of nanoparticles increased, the corresponding MRI signal would be significantly enhanced. It was used in the MR scan of patients with unruptured IA. Nanoparticle solution could increase the visibility of the aneurysm, and the image quality of the aneurysm wall could be significantly enhanced.

Calixarenes functionalised water-soluble iron oxide magnetite nanoparticles for enzyme immobilisation

ABSTRACT In this study, we first used water-soluble iron oxide nanoparticles for Candida rugosa lipase immobilisation. Moreover, two new complexation phenomena of the prepared water-soluble Fe3O4 nanoparticles with an enzyme might address interesting results in terms of enzyme activity and stability in typical enzymatic reactions. The catalytic activity on pH and temperature dependence, and reusability of the immobilised lipases ( p-SCX4-NP-E and p-SCX8-NP-E) were also investigated with the hydrolysis reaction of p-nitrophenyl palmitate (p-NPP). The results show that the highest catalytic affinities for p-SCX4-NP-E and p-SCX8-NP-E were obtained at pH 5.0 and pH 7.0, respectively.

Continuous growth phenomenon for direct synthesis of monodisperse water-soluble iron oxide nanoparticles with extraordinarily high relaxivity.

The direct synthesis of highly water-soluble nanoparticles has attracted intensive interest, but systematic size control has not been reported. Here, we developed a general method for synthesizing monodisperse water-soluble iron oxide nanoparticles with nanometer-scale size increments from 4 nm to 13 nm in a single reaction. Precise size control was achieved by continuous growth in an amphiphilic solvent, diethylene glycol (DEG), where the growth step was separated from the nucleation step by sequential addition of a reactant. There was only one reactant in the synthesis and no need for additional capping agents and reducing agents. This study reveals the "living growth" character of iron oxide nanoparticles synthesised in an amphiphilic solvent. The synthetic method shows high reproducibility. The as-prepared iron oxide nanoparticles are extremely water soluble without any surface modification. Surprisingly, the synthesized 9 nm iron oxide nanoparticles exhibit extremely high transversal and longitudinal relaxivities of 425 mM-1 s-1 and 32 mM-1 s-1 respectively, which is among the highest transversal relaxivity in the literature for sub-10 nm spherical nanoparticles. This study will not only shed light on the continuous growth phenomenon of iron oxide nanoparticles in an amphiphilic solvent, but could also stimulate the synthesis and application of iron oxide nanoparticles. The continuous growth method could be further extended to other materials for the controlled synthesis of water-soluble nanoparticles.

Polyethyleneimine-modified iron oxide nanoparticles: their synthesis and state in water and in solutions of ligands

Water-soluble iron oxide nanoparticles (IONPs) are synthesized from oleate-stabilized particles (IONPs-OA) by replacing oleate moieties with 3,4-dihydroxybenzoic acid (3,4-DHB) and polyethyleneimine (PEI). Investigation of the obtained composite nanoparticles by TEM, SEM, and AFM methods demonstrated that the parent IONPs-OA particles have a narrow size distribution and that the size of the magnetite core (4.3 nm) was retained in the polyethyleneimine modified IONPs-PEI nanoparticles (4.5 nm). IONPs-PEI exist in the form of separate nanoparticles distributed in the bulk polymer matrix as well as elongated chains (up to 20 nm in length) consisting of 3–6 nanoparticles, and mostly in the form of large clusters (~ 150 nm). The NMR relaxometric properties of IONPs-PEI in the water at various pHs are determined. Relaxivity of such modified nanoparticles remains constant over a wide pH range (3–9) and decreases only in strongly alkaline solutions due to the destruction processes. In the presence of physiological amounts of NaCl (0.15 M), the relaxivity of IONPs-PEI solutions is reduced by 37%. The effect of the addition of various iron(III) chelators is analyzed. Tiron (disodium 4,5-dihydroxy-1,3-benzenedisulfonate) is the only ligand which destroys the polymer-bound IONP system in solution, dissolving the iron oxide core, while other ligands (3,4-DHB, 2,4-DHB, citric acid) do not reduce the relaxation of the composite aqueous solution. The developed polyethyleneimine-modified iron oxide nanoparticles can be regarded as a promising model of a contrast agent for magnetic resonance imaging (MRI).

Ethylene diamine-assisted synthesis of iron oxide nanoparticles in high-boiling polyolys

The decomposition of iron(III) acetylacetonate in high-boiling polyols such as diethylene glycole is an efficient way to produce water-soluble iron oxide nanoparticles (IONPs) with small sizes. We present an extension of this method by introducing ethylene diamine (EDA) or diethylene triamine (DTA) as a structure-directing agent and adding polyvinylpyrrolidone (PVP) as a stabilizing agent. The synthesis was studied with respect to effects of the chain length of the polyol used as solvent, the chain length of the structure-directing agent, the presence of PVP, the heating rate, and the nature of the precursor. By varying these parameters, we were able to show, that probably an interplay of the structure-directing agent and the polyol plays an important role for the stabilization and growth of the different facets of the IONP crystal. The chain length of the polyol used as solvent alters the influence of EDA or DTA as stabilizer of {111} facets, leading to IONPs with spherical, tetrahedral, or nanoplate morphology and mean diameters ranging from 4nm up to 25nm. PVP in the reaction medium narrows down particle size and shape distributions and promotes the formation of very stable, water-based colloidal solutions. The saturation magnetization of the particles was determined by a superconducting quantum interference device (SQUID) and their ability to act as a T2-contrast agent was tested by magnetic resonance imaging (MRI).

Functionalization of magnetic nanocrystals by oligo (ethylene oxide) chains carrying diazonium and iniferter end groups

The water stability of iron oxide nanoparticles (NPs) is a major issue for biomedical and biological applications. This paper presents a versatile approach for preparing water-soluble iron oxide nanoparticles coated by bifunctional oligo(ethylene oxide) (OEO) chains, carrying on the one side a diazonium end group for covalent grafting at the NP surface and on the other side an iniferter group (diethyl dithiocarbamate) for initiating the growing of poly(methacrylic acid). The nanoparticles were synthesized by coprecipitation in basic media and functionalized in situ by adding the diazonium salt directly in the synthesis medium. Oligo(ethylene oxide) with various chain lengths (from one to three monomer units) was grafted at the NP surface using this approach. The length of the OEO spacer between the NP surface and the iniferter end group was found to be a critical parameter for controlling the colloidal stability of the hybrid NPs. The polymerization time was also shown to strongly influence their colloidal stability, emphasizing the interest to control the interfacial properties of the hybrids for obtaining stable dispersions in water.

Interconnection of the nervous tissue lesion in the head of the pancreas with the degree of fibrous changes

The water stability of iron oxide nanoparticles (NPs) is a major issue for biomedical and biological applications. This paper presents a versatile approach for preparing water-soluble iron oxide nanoparticles coated by bifunctional oligo(ethylene oxide) (OEO) chains, carrying on the one side a diazonium end group for covalent grafting at the NP surface and on the other side an iniferter group (diethyl dithiocarbamate) for initiating the growing of poly(methacrylic acid). The nanoparticles were synthesized by coprecipitation in basic media and functionalized in situ by adding the diazonium salt directly in the synthesis medium. Oligo(ethylene oxide) with various chain lengths (from one to three monomer units) was grafted at the NP surface using this approach. The length of the OEO spacer between the NP surface and the iniferter end group was found to be a critical parameter for controlling the colloidal stability of the hybrid NPs. The polymerization time was also shown to strongly influence their colloidal stability, emphasizing the interest to control the interfacial properties of the hybrids for obtaining stable dispersions in water.

Make Conjugation Simple: A Facile Approach to Integrated Nanostructures

We report a facile approach to the conjugation of protein-encapsulated gold fluorescent nanoclusters to the iron oxide nanoparticles through catechol reaction. This method eliminates the use of chemical linkers and can be readily extended to the conjugation of biological molecules and other nanomaterials onto nanoparticle surfaces. The key to the success was producing water-soluble iron oxide nanoparticles with active catechol groups. Further, advanced electron microscopy analysis of the integrated gold nanoclusters and iron oxide nanoparticles provided direct evidence of the presence of a single fluorescent nanocluster per protein template. Interestingly, the integrated nanoparticles exhibited enhanced fluorescent emission in biological media. These studies will provide significantly practical value in chemical conjugation, the development of multifunctional nanostructures, and exploration of multifunctional nanoparticles for biological applications.

Synthesis of monodisperse organic- and water-soluble iron oxide nanoparticles using Fe(OH)3 as precursor

The precursors used to prepare high-quality nanoparticles by high-temperature decomposition are expensive and toxic organometallic compounds. Fe(OH)3, an inexpensive and environmentally friendly iron-containing compound, is for the first time introduced to act as an precursor to generate monodisperse iron oxide nanoparticles. The obtained nanoparticles are characterised by transmission electronic microscopy, IR, XRD and vibrating sample magnetometer. Organic-soluble ferromagnetic rod-like and superparamagnetic dot-like nanoparticles with the size ranging from 12 to 25 nm are obtained in a nonpolar solvent by adjusting reaction parameters, such as surfactant concentration and reaction time. Water-soluble nanoparticles can be synthesised when a bipolar solvent is used instead of nonpolar solvent. The results show that Fe(OH)3 is a promising precursor for the high-temperature decomposition method.

Water-Soluble Iron Oxide Nanoparticles with High Stability and Selective Surface Functionality

The water dispensability and stability of high quality iron oxide nanoparticles synthesized in organic solvents are major issues for biomedical and biological applications. In this paper, a versatile approach for preparing water-soluble iron oxide nanoparticles with great stability and selective surface functionality (-COOH, -NH(2), or -SH) was demonstrated. The hydrophobic nanoparticles were first synthesized by the thermal decomposition of an iron oleate complex in organic solvent. Subsequently, the hydrophobic coatings of nanoparticles were replaced with poly(acrylic acid) , polyethylenimine, or glutathione, yielding charged nanoparticles in aqueous solution. Two parameters were found to be critical for obtaining highly stable nanoparticle dispersions: the original coating and the surfactant-to-nanoparticle ratio. These charged nanoparticles exhibited different stabilities in biological buffers, which were directly influenced by the surface coatings. This report will provide significant practical value in exploring the biological or biomedical applications of iron oxide nanoparticles.

Preparation and Evaluation of Magnetic Nanoparticles for Cell Labeling

Cell labeling and tracking are becoming increasingly important in the fields of stem cell transplantation. To track the migration and distribution of the implanted cells is critical for understanding the beneficial effects of stem cell therapy. The aim of this study is to synthesize new superparamagnetic nanoparticles and investigate the feasibility of magnetic labeling of bone marrow mesenchymal stem cells (MSCs). Monodisperse hydrophobic magnetite (Fe3O4) nanoparticles were prepared through high temperature decomposition of Fe(acac)3 and a long-chain alcohol. The nanoparticles were further modified with a bipolar surfactant, 2,3-dimercaptosuccinic acid (DMSA) and then transformed into water-soluble iron oxide nanoparticles (WION). The magnetic particles showed uniform size (10 nm), high efficiency and stability in MSCs labeling. The labeled cells were cultured until passage 8, there is no reduction in magnetic tropism and the percentage of labeled cells. The results of MTT proliferation assay and flow cytometry analysis show that the WION are biocompatible. The labeling process does not cause cell death and apoptosis, and has no side effect on growth capacity of the cells. In conclusion, the successful and stable labeling of MSCs and the efficient magnetic tropism indicate that this WION can be used for tracking of MSCs in future MSCs-based stem cell therapy.

HER2/neu Antibody Conjugated Poly(amino acid)-Coated Iron Oxide Nanoparticles for Breast Cancer MR Imaging

Superparamagnetic iron oxide nanoparticles are widely used as nanoprobes for magnetic resonance imaging (MRI). Water-soluble iron oxide nanoparticles were synthesized by coating iron oxide nanoparticles with a hydrophilic, biocompatible, biodegradable poly(amino acid) derivative, poly(2-hydroxyethyl aspartamide) graft copolymer for negative contrast enhancement on T2 weighted MRI. HER2/neu antibodies were conjugated on the surface of poly(amino acid) coated iron oxide nanoparticles for the detection of breast cancer. The antibody-grafted iron oxide nanoparticles (PAION-Ab) were about 31.1 nm in diameter. The T2 relaxivity of PAION-Ab was 246 L·mmol(-1)·sec(-1) greater than that of the commercial product such as Feridex. PAION-Ab showed low cytotoxicity even at relatively high concentrations. Furthermore, Prussian blue staining and in vitro MRI study with SKBR-3, breast cancer cells overexpressing HER2/neu receptors indicated that PAION-Ab exhibited excellent cancer cell detection ability and enhanced signal intensities in the T2-weighted image.

Preparation and characterization of water-soluble monodisperse magnetic iron oxide nanoparticles via surface double-exchange with DMSA

A simple, but efficient method for preparation of water-soluble iron oxide nanoparticles has been developed. Monodisperse Fe 3O 4 nanoparticles were synthesized by thermal decomposition of iron-oleate. Surface double-exchange of oleic acid capped monodisperse Fe 3O 4 nanoparticles with a familiar 2,3-dimercaptosuccinnic acid (HOOC–CH(SH)–CH(SH)–COOH, DMSA) was first performed in chloroform in the presence of triethylamine, and then this process was repeated in ethanol under the same conditions. The resulting Fe 3O 4 nanoparticles could be transferred into water to form stable magnetic fluid without post-treatment processes such as filtration and re-concentration. TEM images show that water-soluble Fe 3O 4 nanoparticles remain monodisperse and even form a monolayer of ordered assembly, and the results of TGA, VSM show that Fe 3O 4 nanoparticles via surface double-exchange possess more DMSA molecules through intermolecular disulfide cross-linking between DMSA, as confirmed by Raman spectra. Zeta potential measurements show that nanoparticles after surface double-exchange are negatively charged in the range of pH = 1–14, and stability assays exhibit their excellent stability in water and other physiological environments.

Formation of Water-Soluble Iron Oxide Nanoparticles Derived from Iron Storage Protein

This paper reports novel findings of an investigation of the formation of water-soluble iron oxide nanoparticles from iron-storage protein ferritin. The strategy couples thermal removal of the protein shell on a planar substrate and subsequent sonication in aqueous solution under controlled temperature. Advantages of using ferritin as a precursor include well-defined core size, core composition, water-solubility and processibility. The formation of the nanoparticles was characterized using TEM, UV-Vis and FTIR techniques. Iron oxide nanoparticles in the size range of 5-20 nm diameters were produced. In addition to thermal treatment conditions, the sonication temperature of the nanoparticles in water was found to play an important role in determining the resulting particle size. This simple and effective route has important implications to the design of composite nanoparticles for potential magnetic, catalytic, biomedical sensing and other nanotechnological applications.