Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles

Stable 30–50 nm polymeric polyethylene glycol–phosphatidylethanolamine (PEG–PE)-based micelles entrapping superparamagnetic iron oxide nanoparticles (SPION) have been prepared. At similar concentrations of SPION, the SPION-micelles had significantly better magnetic resonance imaging (MRI) T2 relaxation signal compared to ‘plain’ SPION. Freeze-fracture electron microscopy confirmed SPION entrapment in the lipid core of the PEG–PE micelles. To enhance the targeting capability of these micelles, their surface was modified with the cancer cell-specific anti-nucleosome monoclonal antibody 2C5 (mAb 2C5). Such mAb 2C5-SPION immunomicelles demonstrated specific binding with cancer cells in vitro and were able to bring more SPION to the cancer cells thus demonstrating the potential to be used as targeted MRI contrast agents for tumor imaging.     

Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F₅-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F₅-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.     

Temperature dependence of superparamagnetic resonance of iron oxide nanoparticles

Nanoparticles of maghemite (γ-Fe₂O₃) are formed in a sol–gel silicate glass with a molar ratio Fe/Si of 2% by a treatment at 1000°C for 6 h. Electron paramagnetic resonance spectrum at 300 K shows a relatively narrow sharp line at g_eff≈2. As the temperature lowers to 5 K, the apparent resonance field decreases and the linewidth considerably increases. We develop a theoretical formalism based on a distribution of diameters or volumes of the nanoparticles following a lognormal. The nanoparticles are considered as single magnetic domains with random orientations of magnetic moments and thermal fluctuations of anisotropic axes. The individual line shape function is derived from the damped precession equation of Landau–Lifshitz. An appropriate linewidth expression is put forward, which account for the averaging of the fluctuations of orientations of the magnetic moments with respect to the magnetic field and to the magnetic anisotropy axes. A single set of parameters provides good fits to the spectra recorded at the different temperatures. The low-temperature blocking of the nanoparticle magnetic moments has been clearly evidenced in the resonance absorption intensity and the blocking temperature of the assembly of nanoparticles (averaged over the distribution in the nanoparticle volume) has been evaluated as 90 K.     

Synthesis and characterization of superparamagnetic iron oxide nanoparticles for biomedical applications

Monodisperse iron oxide nanoparticles (NPs) of 4 nm were obtained through high-temperature solution phase reaction of iron (III) acetylacetonate with 1, 2-hexadecanediol in the presence of oleic acid and oleylamine. The as-synthesized iron oxide nanoparticles have been characterized by X-ray diffraction, transmission electron microscopy, Mössbauer spectroscopy and magnetic measurements. The species obtained were Fe₃O₄ and/or $\upgamma$ -Fe₂O₃. These NPs are superparamagnetic at room temperature and even though the reduced particle size they show a high saturation magnetization (MS ≈ 90 emu/g).     

Covalent immobilization of invertase on PAMAM-dendrimer modified superparamagnetic iron oxide nanoparticles

In this study, polyamidoamine (PAMAM) dendrimer was synthesized on the surface of superparamagnetite nanoparticles to enhance invertase immobilization. The amount of immobilized enzyme on the surface-hyperbranched magnetite nanoparticle was up to 2.5 times (i.e., 250%) as much as that of magnetite nanoparticle modified with only amino silane. Maximum reaction rate (V _max) and Michaelis–Menten constant (K _m) were determined for the free and immobilized enzymes. Various characteristics of immobilized invertase such as; the temperature activity, thermal stability, operational stability, and storage stability were evaluated and results revealed that stability of the enzyme is improved upon immobilization.     

Inflammatory imaging with ultrasmall superparamagnetic iron oxide

The purpose of this study was to investigate the usefulness and feasibility of magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) (USPIO-enhanced MRI) for imaging inflammatory tissues. First, we investigated the relationship between the apparent transverse relaxation rate (R2*) and the concentration of USPIO by phantom studies and measured the apparent transverse relaxivity (r2*) of USPIO. Second, we performed animal experiments using a total of 30 mice. The mice were divided into five groups [A (n=6), B (n=6), C (n=6), sham control (n=6), and control (n=6)]. The mice in Groups A, B, C and control were subcutaneously injected with 0.1 ml of turpentine oil on Day 0, while those in the sham control group were subcutaneously injected with 0.1 ml of saline. The mice in Groups A, B, C and sham control were intraperitoneally injected with 200 μmol Fe per kilogram body weight of USPIO (28 nm in diameter) immediately after the first MRI study on Days 3, 5, 7 and 7, respectively, and those in the control group were not injected with USPIO. The second and third MRI studies were performed at 24 and 48 h after USPIO administration, respectively. The maps of R2* were generated from the apparent transverse relaxation time (T2*)-weighted images with six different echo times. The phantom studies showed that there was a linear relationship between R2* and the concentration of USPIO (r=0.99) and the r2* value of USPIO was 105.7 mM⁻¹ s⁻¹. There was a significant increase of R2* in inflammatory tissues in Group C at 24 h after USPIO administration compared with the precontrast R2* value. Our results suggest that USPIO-enhanced MRI combined with R2* measurement is useful for detecting inflammatory tissues.     

Incorporation and release of drug into/from superparamagnetic iron oxide nanoparticles

The aim of this study was to attach a model drug (naproxen) onto superparamagnetic iron oxide nanoparticles (SPION). First, SPION were coated with thin layer of silica that contained micropores. We demonstrated that such surface functionalization could be optimized by the use of citric acid which prevented SPION agglomeration during the procedure. HRTEM investigation showed a uniform 1-2-nm-thick silica coating around SPION. This coating did not affect significantly the magnetic properties of the SPION. Into the coated SPION we successfully incorporated about 30 wt% of naproxen. The latter was readily released after immersion into a testing solution. The composites could be interesting for potential use in diagnostics.     

Application of factor analysis to XPS valence band of superparamagnetic iron oxide nanoparticles

X-Ray photoelectron spectra of nano-sized superparamagnetic iron oxide nanoparticles were examined with the aim to discriminate the different degree of iron oxidation. Careful analysis of the valence band regions reveals the presence of both Fe₃O₄ and Fe₂O₃. The application of factor analysis enabled us to extract the relative molar concentrations of these oxides in the nanoparticles. This is of particular interest in improving the magnetic properties of iron oxide nanoparticles whose superparamagnetic character can be optimized to obtain better contrast in images from nuclear magnetic resonance. As a result, the factor analysis allows tuning the nanoparticle synthesis conditions in order to obtain the optimal magnetic properties for imaging. Results obtained by the XPS valence band analysis were compared to the transmission electron microscopy, X-ray diffraction and Raman measurements.     

Toxicity of superparamagnetic iron oxide nanoparticles: Research strategies and implications for nanomedicine

Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.     

Synthesis of amino-group functionalized superparamagnetic iron oxide nanoparticles and applications as biomedical labeling probes

Superparamagnetic iron oxide (SPIO) nanoparticles were synthesized by coprecipitation technique and further functionalized with amino-group to obtain amino-group functionalized (amino-SPIO) nanoparticles. The X-ray diffraction results reveal the structure of amino-SPIO nanoparticles, from which the average iron core diameter is approximately 10 nm by calculation; while Zetasizer reveals their hydrodynamic diameter are mainly distributed in the range of 40?C60 nm. These nanoparticles can be taken up by liver tissue, resulting in dramatically darkening of liver tissue under T2-magnetic resonance imaging (MRI). The spin?Cspin relaxivity coefficient of these nanoparticles is 179.20 mM^?1 s^?1 in a 1.5 T magnetic resonance system. In addition, amino-SPIO nanoparticles were conjugated to Tat (FITC) peptide and incubated with neural stem cells in vitro, the authors can detect the positive-labeling (labeled) neural stem cells showing green fluorescence, which indicates Tat (FITC) peptide-derivated amino-SPIO nanoparticles are able to enter cells. Furthermore, it was also find significant negative T2 contrast enhancement when compared with the non-nanoparticles-labeled neural stem cells in T2-weighted MRI. The amino-SPIO nanoparticles show promising potential as a new type of labeling probes, which can be used in magnetic resonance-enhanced imaging and fluorescence diagnosis.     

Magnetic composites based on hybrid spheres of aluminum oxide and superparamagnetic nanoparticles of iron oxides

Materials containing hybrid spheres of aluminum oxide and superparamagnetic nanoparticles of iron oxides were obtained from a chemical precursor prepared by admixing chitosan and iron and aluminum hydroxides. The oxides were first characterized with scanning electron microscopy, X-ray diffraction, and Mössbauer spectroscopy. Scanning electron microscopy micrographs showed the size distribution of the resulting spheres to be highly homogeneous. The occurrence of nano-composites containing aluminum oxides and iron oxides was confirmed from powder X-ray diffraction patterns; except for the sample with no aluminum, the superparamagnetic relaxation due to iron oxide particles were observed from Mössbauer spectra obtained at 298 and 110 K; the onset six line-spectrum collected at 20 K indicates a magnetic ordering related to the blocking relaxation effect for significant portion of small spheres in the sample with a molar ratio Al:Fe of 2:1.     

One-pot reaction to synthesize superparamagnetic iron oxide nanoparticles by adding phenol as reducing agent and stabilizer

An improved thermal decomposition method was used to directly prepare water-soluble Fe₃O₄ magnetic nanoparticles (MNPs) with relatively higher quality via reductive decomposition of ferric acetylacetonate [Fe(acac)₃], in the presence of benzyl ether and phenol, in which inexpensive phenol acted as reducing agent and stabilizer, produce the semi phenol-benzoquinone coated on the Fe₃O₄ and make the Fe₃O₄·MNPs water-soluble and the colloidal solution stable. By changing the molar ratio of phenol to Fe(acac)₃ and reaction time, the size of Fe₃O₄·MNPs could be varied from 19.3 ± 4.4 nm to 9.7 ± 1.5 nm, with the saturation magnetizations in the range of 51.3–62.9 emu/g.     

Size-controlled synthesis of superparamagnetic iron oxide nanoparticles and their surface coating by gold for biomedical applications

The size mono-dispersity, saturation magnetization, and surface chemistry of magnetic nanoparticles (NPs) are recognized as critical factors for efficient biomedical applications. Here, we performed modified water-in-oil inverse nano-emulsion procedure for preparation of stable colloidal superparamagnetic iron oxide NPs (SPIONs) with high saturation magnetization. To achieve mono-dispersed SPIONs, optimization process was probed on several important factors including molar ratio of iron salts [Fe³⁺ and Fe²⁺], the concentration of ammonium hydroxide as reducing agent, and molar ratio of water to surfactant. The biocompatibility of the obtained NPs, at various concentrations, was evaluated via MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and the results showed that the NPs were non-toxic at concentrations <0.1 mg/mL. Surface functionalization was performed by conformal coating of the NPs with a thin shell of gold (∼4 nm) through chemical reduction of attached gold salts at the surface of the SPIONs. The Fe₃O₄ core/Au shell particles demonstrate strong plasmon resonance absorption and can be separated from solution using an external magnetic field. Experimental data from both physical and chemical determinations of the changes in particle size, surface plasmon resonance optical band, phase components, core–shell surface composition, and magnetic properties have confirmed the formation of the mono-dispersed core–shell nanostructure.     

Synthesis of carboxyl superparamagnetic ultrasmall iron oxide (USPIO) nanoparticles by a novel flocculation-redispersion process

We report a novel flocculation-redispersion method to synthesize and purify the biocompatible superparamagnetic ultrasmall iron oxide (USPIO) nanoparticles coated with carboxyl dextran derivative. First, USPIO nanoparticles were synthesized and flocculated to form the large clusters through bridging effect of polyvinyl alcohol (PVA) during coprecipitation process. Then the flocculated USPIO was separated and purified from the solution conveniently through magnetic sedimentation. Finally, USPIO in the clusters were released again and well dispersed through electrostatic repelling effect of citric acid with the aid of ultrasonic. The dispersed carboxyl-functionalized USPIO was conjugated with the monoclonal antibodies. And it has been proved that the antibodies anchored on USPIO still retained their bioactivity after the conjugation. These results implied that the USPIO synthesized have good potential as active targeting molecular probe in biomedical application.     

Optimization of sonochemical method of functionalizing Amino-Silane on superparamagnetic iron oxide nanoparticles using Central Composite Design

Optimization of sonochemical method of functionalizing a Silane coupling agent, Amino-Silane on Superparamagnetic Iron Oxide Nanoparticles (SPION) using Central Composite Design is reported. The Amino-Silane is grafted on the SPION in an iced bath environment using a Vibra-Cell 20 kHz ultrasonic irradiator with 13 mm diameter horn. Throughout the experiment amplitude of the ultrasonic device is maintained at 47%. The percentage atomic compositions of various APTES elements which bind to the SPION due to the ultrasonic irradiation were determined using X-ray photoelectron spectrometer (XPS). The influence of ultrasonic irradiation time and amount of APTES required for facile, rapid and effective functionalization of Organo-metallic compound on SPION are optimized. The optimized sonication time and amount of APTES are 8.49 min and 3.40 ml, respectively. The predicted results were validated with experimental data. Using the optimized values APTES were functionalized on the SPION experimentally and the results were compared. The experimental results validate the predicted data. Results show that very minimum sonication time is required for effective grafting of APTES on SPION.     

Synthesis,characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T ₂ contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T ₂ relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.     

Characterization of PEI-coated superparamagnetic iron oxide nanoparticles for transfection: Size distribution,colloidal properties and DNA interaction

Superparamagnetic iron oxide nanoparticles (SPIONs) were coated with polyethylenimine. Here, we briefly describe the synthesis as well as DNA:PEI:SPION complexes and the characterization of the compounds according to their particle size, ζ-potential, morphology, DNA complexing ability, magnetic sedimentation, and colloidal stability. PEI coating of SPIONs led to colloidally stable beads even in high salt concentrations over a wide pH range. DNA plasmids and PCR products encoding for green fluorescent protein were associated with the described beads. The complexes were added to cells and exposed to permanent and pulsating magnetic fields. Presence of these magnetic fields significantly increased the transfection efficiency.     

How size evaluation of lymph node is protocol dependent in MRI when using ultrasmall superparamagnetic iron oxide nanoparticles

In this study, the volume of susceptibility artifact was evaluated in T1 and T2-weighted spin echo (SE) and gradient echo (GRE) images at various parameters using registration and subtraction methods. In order to state an important misinterpretation problem in lymphography, it was demonstrated that a lymph node size may be enlarged approximately 10 times when a T2*-weighted GRE protocol is used. To overcome this problem a technical consideration using multisequence (GRE and SE) paradigm was suggested to ensure both lymph node detection and metastasis identification in lymphatic system. The paradigm was also extended by post-processing manipulation of the SE images using a registration and subtraction approach for detection of lymphatic lesions.     

Tannin biosynthesis of iron oxide nanoparticles

In this work, iron oxide nanoparticles synthesized with gallic acid and tannic acid are characterized using High-Resolution Transmission Electron Microscopy (HRTEM). Its size, form, and structure are compared with nanoparticles obtained previously using alfalfa biomass in order to find a simpler, consistent, and environmentally friendly method in the production of iron oxide nanoparticles.     

Characterization of magnetic iron oxide nanoparticles

Magnetic nanoparticles have promising applications in many areas, for example optics, electronics, biology, medicine, etc. The main goal of this study is to synthezise and characterize ε-Fe₂O₃ magnetic nanoparticles embedded in amorphous SiO₂ matrix. The Mössbauer spectroscopy analysis of the samples was complemented by the study of X-ray powder diffraction and high-resolution transmission electron microscopy.