Development of citrate-stabilized Fe3O4 nanoparticles: Conjugation and release of doxorubicin for therapeutic applications

We demonstrate a single-step facile approach for the fabrication of citric acid functionalized (citrate-stabilized) Fe₃O₄ aqueous colloidal magnetic nanoparticles (CA-MNP) of size 8-10 nm using soft chemical route. The surface functionalization of Fe₃O₄ nanoparticles with citric acid was evident from infrared spectroscopy, thermal and elemental analyses, and zeta-potential measurements. The drug-loading efficiency of CA-MNP was investigated using doxorubicin hydrochloride (DOX) as a model drug to evaluate their potential as a carrier system. The quenching of fluorescence intensity and decrease in surface charge of drug loaded CA-MNP strongly suggest the interaction/attachment of drug molecules with CA-MNP. More specifically, the present investigation discusses a method for entrapping positively charged drugs onto the surface of negatively charged CA-MNP through electrostatic interactions and suggests that bound drug molecules will be released in appreciable amounts in the mild acidic environments of the tumors. Furthermore, the aqueous colloidal stability, optimal magnetization, good specific absorption rate (under external AC magnetic field) and cytocompatibility with cells suggested that CA-MNP is appropriate candidate for biomedical applications.     

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.     

Probing temperature-sensitive behavior of pNIPAAm-coated iron oxide nanoparticles using frequency-dependent magnetic measurements

Ferromagnetic iron oxide nanoparticles of about 33 nm in diameter were synthesized by high-temperature decomposition of an iron-oleate complex, using octadecene as the solvent. These particles were subsequently coated with polyN-isopropylacrylamide (pNIPAAm) by a surfactant exchange method. Temperature-sensitive behavior of these particles was studied using ac susceptibility and dynamic light scattering (DLS) measurements. Shifts in the imaginary part of the ac susceptibility are correlated with swelling and collapse of pNIPAAm as a function of temperature.     

Particle size dependence of relaxivity for silica-coated iron oxide nanoparticles

We investigate the particle size dependence of the relaxivity of hydrogen protons in an aqueous solution of iron oxide (Fe₃O₄) nanoparticles coated in silica for biocompatibility. The T₁ and T₂ relaxation times for various concentrations of silica-coated nanoparticles were determined by a magnetic resonance scanner. We find that the relaxivity increased linearly with increasing particle size. The T₂ relaxivity (R₂) is more than 50 times larger than the T₁ relaxivity (R₁) for the nanoparticle contrast agent, which reflects the fact that the T₂ relaxation is mainly influenced by outer sphere processes. The high R₂/R₁ ratio demonstrates that silica-coated iron oxide nanoparticles may serve as a T₂ contrast agents in magnetic resonance imaging with high efficacy.     

Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI

Superparamagnetic iron oxide particles (SPIOs) are usually referred to as T₂ MR contrast agents, reducing signal intensity (SI) on T₂-weighted MR images (negative enhancement). This study reports the original use of SPIOs as T₁-enhancing contrast agents, primarily assessed in vitro, and then applied to an in vivo investigation of a myocardial perfusion defect. Using a strongly T₁-weighted subsecond MR sequence with SPIOs intravenous (IV) bolus injection, MR imaging of myocardial vascularization after reperfusion was performed, on a dog model of coronary occlusion followed by reperfusion. Immediately after the intravenous bolus injection of 20 μmol/kg of SPIOs, a positive signal intensity enhancement was observed respectively, in the right and left ventricular cavity and in the nonischemic left myocardium. Moreover, compared to normal myocardium, the remaining ischemic myocardial region (anterior wall of the left ventricle) appeared as a lower and delayed SI enhancing area (cold spot). Mean peak SIE in the nonischemic myocardium (posterior wall) was significantly higher than in the ischemic myocardium (anterior wall) (110 ± 23% vs. 74 ± 22%, Mann-Whitney test < 1%, n₁ = 6, n₂ − n₁ = 0, U > 2). In conclusion, the T₁ effect of SPIOs at low dose, during their first intravascular distribution, suggests their potential use as positive markers to investigate the regional myocardial blood flow and some perfusion defects such as the “no-reflow phenomenon”.     

Diffusion-weighted imaging versus superparamagnetic iron oxide (SPIO)-enhanced MRI: exclusive and combined values in the assessment of hepatic metastases

Purpose

The purpose was to validate diffusion-weighted imaging (DWI) in the assessment of hepatic metastases compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging.

Materials and Methods

For 21 consecutive patients with 160 metastases from extrahepatic malignancy and 25 benign focal lesions, two radiologists evaluated four separate review sessions (I, SPIO-enhanced T2?-weighted images; II, precontrast DWI; III, SPIO-enhanced T2?-weighted images and precontrast DWI; IV, SPIO-enhanced T2?-weighted images plus precontrast and SPIO-enhanced DWI) and assigned confidence levels using a five-grade scale for each hepatic lesion.

Results

The A_z values after receiver operating characteristic curve analysis for Reader 1 and Reader 2 were 0.80 and 0.75 on session I, 0.91 and 0.91 on session II, 0.97 and 0.96 on session III and 0.96 and 0.96 on session IV, respectively. The A_z value of session II was significantly higher than that of session I (Reader 1, P=.004; Reader 2, P<.001), and that of session III was significantly higher than that of session I (P<.001 for each reader) or session II (Reader 1, P=.004; Reader 2, P=.003). Although there was no significant difference of A_z value between session III and session IV (Reader 1, P=.231; Reader 2, P=.878), the sensitivity improved for session IV compared with that for session III (Reader 1, P=.031; Reader 2, P=.039).

Conclusion

In the assessment of hepatic metastases, DWI can provide more accurate information than can SPIO-enhanced images. Diagnostic accuracy can be increased even more through the combination of both techniques.     

Photoelectron escape from iron oxide

Iron oxide of nanometer thickness were grown in situ by step-by-step oxidation of an iron foil to measure the escape probabilities of O 1s photoelectrons as a function of depth of origin, the so-called emission depth distribution function (EDDF), and the mean escape depth (MED). To record photoelectron spectra for a wide range of emission angles, the X-ray excitation source was positioned on the opposite side of the iron foil with respect to the analyzer. To excite photoelectrons on the side of the foil surface adjacent to the analyzer, the foil was made thin enough to be semitransparent to the X-ray radiation. The O 1s spectra were recorded for a wide range of oxide thicknesses until no features of metallic iron were recognized in the photoelectron spectra. The escape probability of the O 1s photoelectrons in the iron oxide was derived from the oxide-thickness dependence of the O 1s peak areas. The resulting EDDF reached a maximum beneath the oxide surface for X-ray incidence and electron-emission angles located along the surface normal. For the same incidence angle and an emission angle of 60°, the escape probability could be well approximated by a simple exponential function. The mean escape depths were obtained for both experimental geometries and agreed well with the available theory.     

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.     

A new method for preparation of magnetite from iron oxyhydroxide or iron oxide and ferrous salt in aqueous solution

In this study, a new method is proposed for the preparation of Fe₃O₄ from iron oxyhydroxides (goethite, akaganeite, lepidocrocite, feroxyhyte and ferrihydrite) or iron oxide (hematite) and ferrous salt in aqueous solution. The product is magnetite with various particle sizes. Products are characterized by X-ray powder diffraction, IR spectra and vibrating sample magnetometery.     

Phase transfer of highly monodisperse iron oxide nanocrystals with Pluronic F127 for biomedical applications

Iron oxide nanoparticles made from the thermal decomposition method are highly uniform in all respects (size, shape, composition and crystallography), making them ideal candidates for many bioapplications. The surfactant coating on the as-synthesized nanoparticles renders the nanoparticles insoluble in aqueous solutions. For biological applications nanoparticles must be water soluble. Here we demonstrate the phase transfer of our nanoparticles with the biocompatible copolymer Pluronic F127. Transmission electron microscopy, Fourier transform infrared spectroscopy and dynamic light scattering indicate that the nanoparticles are coated discretely. Magnetic measurements show that the nanoparticles remain superparamagnetic with saturation magnetization ∼96% of the maximum theoretical value.     

Synthesis and rheological properties of an iron oxide ferrofluid

A ferrofluid (FF) was synthesized in air using a co-precipitation method. Some rheological properties and magnetoviscous effects of this sample were studied. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used for characterization of the solid particles, and the rheological properties were investigated with a special rheometer with variable magnetic field. Magnetic particles with mean particle size of 10.6 nm were obtained. Rheological results show that the shear thinning behavior in the absence and presence of magnetic field is different from that based fluid behavior. Moreover, contrary to expectation, the magnetoviscous effect showed an initial increase at low shear rates (near 15 s⁻¹) and decrease at higher shear rates. The rheological properties of FF depend on the rearrangement of nanoparticles. In addition, time is an effective factor in the formation and destruction of magnetically induced structures.     

Magnetic iron oxide nanoclusters with tunable optical response

We have developed a modified synthetic protocol for the growth of monodispersed, superparamagnetic, flower-like colloidal nanoclusters (CNCs), which are consisted of smaller iron oxide nanocrystals with adjustable size. We show that their optical properties can be tuned by applying an external magnetic field. The latter controls the subtle balance of the CNCs’ mutual interactions (magnetic versus electrostatic) and drives their assembly in aqueous media. Spectrophotometric measurements reveal that a diffuse reflectance maximum, in the visible range, is related to the CNCs organization. As the strength of the external magnetic field increases, in the range 160–600 G, the spectral weight of this feature shifts towards the blue region of the spectrum. The induced photonic crystal-like response entails a remarkable magneto-optical behavior, closely associated with the size-dependent characteristics of the CNCs ensemble. Such materials pave the way for promising technological implementations in photonics.     

Influence of the ultrasound cavitation intensity on reduced graphene oxide functionalization

Graphene is a valuable and useful nanomaterial due to its exceptionally high tensile strength, electrical conductivity and transparency, as well as the ability to tune its materials properties via functionalization. One of the most important features needed to integrate functionalized graphene into products via scalable processing is the effectiveness of graphene dispersion in aqueous and organic solvents. In this study, we aimed to achieve the functionalization of reduced graphene oxide (rGO) by sonication in a one-step process using polyvinyl alcohol (PVA) as a model molecule to be bound to the rGO surface. We investigated the influence of the sonication energy on the efficacy of rGO functionalization. The correlation between the performance of the high-intensity ultrasonic horn and the synthesis of the PVA functionalized rGO was thoroughly investigated by TGA coupled with MS, and IR, Raman, XPS, Laser diffraction, and SEM analysis. The results show that the most soluble PVA-functionalized rGO is achieved at 50% of the ultrasonic horn amplitude. Analysis of cavitation dynamics revealed that in the near vicinity of the horn it is most aggressive at the highest amplitude (60%). This causes rGO flakes to break into smaller domains, which negatively affects the functionalization process. On the other hand, the maximum of the pressure pulsations far away from the horn is reached at 40% amplitude, as the pressure oscillations are attenuated significantly in the 2-phase flow region at higher amplitudes. These observations corelate well with the measured degree of functionalization, where the optimum functionalized rGO dispersion is reached at 50% horn amplitude, and generally imply that cavitation intensity must be carefully adjusted to achieve optimal rGO functionalization.     

One-step preparation of hierarchical superparamagnetic iron oxide/graphene composites via hydrothermal method

In this paper, graphene/magnetite composites with hierarchical Fe₃O₄ structures were synthesized via a one-step hydrothermal method. The size of Fe₃O₄ nanocrystals and nanocrystal clusters can easily be controlled by altering reaction time and the starting mixed solvent ratio, respectively. Raman measurements evidenced that graphene oxide was simultaneously reduced to graphene during the deposition of magnetite particles. The deposition of Fe₃O₄ nanocrystals and nanocrystal clusters impedes graphene to restore the graphite structure. The composites showed a high crystallinity of magnetite and a considerable saturation magnetization. Furthermore, the acrylate modified Fe₃O₄ makes the composites water-dispersible and can effectively load polyfluorene polyelectrolyte via electrostatic force. The high magnetism, excellent water dispersibility and strong photoluminescence make these composites ideal candidates for various important applications such as magnetic resonance imaging, bioseparation, bioimaging, and optical devices fabrication.     

Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging

The goal of this study was to optimize and validate a combined spin- and gradient-echo (SAGE) sequence for dynamic susceptibility-contrast magnetic resonance imaging to obtain hemodynamic parameters in a preclinical setting. The SAGE EPI sequence was applied in phantoms and in vivo rat brain (normal, tumor, and stroke tissue). Partial and full Fourier encoding schemes were implemented and characterized. Maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), vessel size index (VSI), volume transfer constant (K^trans), and volume fraction of the extravascular extracellular space (v_e) were obtained. Partial Fourier encoding provided shortened echo times with acceptable signal-to-noise ratio and temporal stability, thus enabling reliable characterization of T₂, T₂^? and T₁ in both phantoms and rat brain. The hemodynamic parameters CBV, CBF, and MTT for gradient-echo and spin-echo contrast were determined in tumor and stroke; VSI, K^trans, and v_e were also computed in tumor tissue. The SAGE EPI sequence allows the acquisition of multiple gradient- and spin-echoes, from which measures of perfusion, permeability, and vessel size can be obtained in a preclinical setting. Partial Fourier encoding can be used to minimize SAGE echo times and reliably quantify dynamic T₂ and T₂^? changes. This acquisition provides a more comprehensive assessment of hemodynamic status in brain tissue with vascular and perfusion abnormalities.     

Structural and optical properties of porous iron oxide

The structural and optical properties of the novel porous iron oxide fabricated by wood template have been investigated. The obtained porous iron oxide was characterized to be α- Fe₂O₃ by Fourier transform infrared and Raman spectroscopy. X-ray absorption fine structure measurement revealed that the bond length of Fe-O₁ of the porous iron oxide has good agreement with that reported for the α- Fe₂O₃ crystal structure while the bond lengths for Fe-O₂ and Fe-Fe deviate slightly from those of the α- Fe₂O₃ crystal structure. Photoluminescence from the porous iron oxide exhibited broad emission bands around 760 and 890 nm, which are believed to be due to the unique nanoscale structure of the porous iron oxide.     

Synthesis of α- and β-FeOOH iron oxide nanoparticles in non-ionic surfactant medium

Forced hydrolysis of Fe(III) ions in acidic media was performed under controlled synthetic conditions to produce α- and β-FeOOH iron oxides. The forced hydrolysis synthesis was carried out, separately, in an aqueous medium and the lamellar lyotropic liquid crystalline phase of a commercial non-ionic surfactant/water system. The FT-IR analyses confirmed formation of α- and β-FeOOH iron oxides in the aqueous and the surfactant media with slight formation of ferrihydrite and haematite. TEM micrographs have shown that particles formed in the lamellar lyotropic phase are smaller than those produced in the aqueous medium with their smallest size dimension being constrained in the nanometre scale with a size ranging between 5 and 100 nm. Particles produced in the nanoscale size appeared to have different optical properties compared to their counterparts produced in the microscale size.     

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.     

Magnetorheology of colloidal dispersion containing Fe nanoparticles synthesized by the arc-plasma method

Spherical crystalline Fe nanoparticles, ∼100 nm in diameter, were synthesized under Ar-50% H₂ arc-plasma. These nanoparticles were dispersed in silicone oil after silane treatment on as-grown thin oxide layer (∼2 nm) to make their surfaces hydrophobic. The resulting Fe nanoparticles exhibited a high saturation magnetization of ∼190 emu/g at room temperature. The static magnetorheological behavior was measured for the colloidal dispersion (solid concentration: 15 vol%) at room temperature under magnetic flux densities of 0-0.3 T, using a parallel-plate-type commercial rheometer. The yield stress continuously increased with magnetic flux density, demonstrating the Bingham plastic behavior. Moreover, subjecting the sample to a magnetic flux density of 0.3 T increased the yield stress by ∼10². Additionally, the colloidal dispersion exhibited good stability against sedimentation.     

Preparation, characterization and properties of novel covalently surface-functionalized zinc oxide nanoparticles

Novel covalently surface-modified zinc oxide (ZnO) nanoparticles (NP) (ZHIE) were successfully prepared, which have organic chains composed of hydrophilic amide and urethane linkages, and terminal amino groups on the surfaces, using zinc acetate monohydrate. FTIR spectroscopy, X-ray analysis and TEM observation suggested that the resultant ZHIE NPs have the mean sizes of about 10 nm in diameters, the organic chains linking the amino groups in the terminals and wurtzite crystal structure. UV-vis absorption spectrum of the ZHIE NPs in methanol showed maximum absorption band at 348 nm, supporting the TEM observations. Photoluminescent spectrum measurements depicted that the ZHIE NPs show broad visible emission band on the basis of trapped-electron emission. Cytotoxicity and phagocytosis assays suggested that the ZHIE NPs are noncytotoxic, and the ZHIE-labeled zymosan particles derived by conjugation of the ZHIE NPs with zymosan are internalized into the cells and generate fluorescence based on the ZHIE NPs.