Formation Mechanism of Maghemite Nanoflowers Synthesized by a Polyol-Mediated Process.

Magnetic nanoparticles are being developed as structural and functional materials for use in diverse areas, including biomedical applications. Here, we report the synthesis of maghemite (γ-Fe2O3) nanoparticles with distinct morphologies: single-core and multicore, including hollow spheres and nanoflowers, prepared by the polyol process. We have used sodium acetate to control the nucleation and assembly process to obtain the different particle morphologies. Moreover, from samples obtained at different time steps during the synthesis, we have elucidated the formation mechanism of the nanoflowers: the initial phases of the reaction present a lepidocrocite (γ-FeOOH) structure, which suffers a fast dehydroxylation, transforming to an intermediate "undescribed" phase, possibly a partly dehydroxylated lepidocrocite, which after some incubation time evolves to maghemite nanoflowers. Once the nanoflowers have been formed, a crystallization process takes place, where the γ-Fe2O3 crystallites within the nanoflowers grow in size (from ∼11 to 23 nm), but the particle size of the flower remains essentially unchanged (∼60 nm). Samples with different morphologies were coated with citric acid and their heating capacity in an alternating magnetic field was evaluated. We observe that nanoflowers with large cores (23 nm, controlled by annealing) densely packed (tuned by low NaAc concentration) offer 5 times enhanced heating capacity compared to that of the nanoflowers with smaller core sizes (15 nm), 4 times enhanced heating effect compared to that of the hollow spheres, and 1.5 times enhanced heating effect compared to that of single-core nanoparticles (36 nm) used in this work.

Degradation of magnetic nanoparticles mimicking lysosomal conditions followed by AC susceptibility.

BACKGROUND: A deeper knowledge on the effects of the degradation of magnetic nanoparticles on their magnetic properties is required to develop tools for the identification and quantification of magnetic nanoparticles in biological media by magnetic means. METHODS: Citric acid and phosphonoacetic acid-coated magnetic nanoparticles have been degraded in a medium that mimics lysosomal conditions. Magnetic measurements and transmission electron microscopy have been used to follow up the degradation process. RESULTS: Particle size is reduced significantly in 24 h at pH 4.5 and body temperature. These transformations affect the magnetic properties of the compounds. A reduction of the interparticle interactions is observed just 4 h after the beginning of the degradation process. A strong paramagnetic contribution coming from the degradation products appears with time. CONCLUSIONS: A model for the in vivo degradation of magnetic nanoparticles has been followed to gain insight on the changes of the magnetic properties of iron oxides during their degradation. The degradation kinetics is affected by the particle coating, in our case being the phosphonoacetic acid-coated particles degraded faster than the citric acid-coated ones.

Large scale production of biocompatible magnetite nanocrystals with high saturation magnetization values through green aqueous synthesis.

In this work, a straightforward aqueous synthesis for mass production (up to 20 g) of uniform and crystalline magnetite nanoparticles with core sizes between 20 and 30 nm, which are the optimum nanoparticle core sizes for hyperthermia applications, is proposed. Magnetic and heating properties have been analyzed showing very high saturation magnetization and magnetic heating values. To stabilize the naked magnetite nanocrystals at physiological pH and increase their circulation time in blood, they have been covalently coated with carboxymethyl dextran, a biocompatible polymer. The influence of this superficial modification on the magnetic and heating properties has been studied showing that these biocompatible magnetic nanocrystals maintain high saturation magnetization values, good colloidal stability and hyperthermia properties in the presence of the polymeric external layer. These particles, suitably functionalized, could be used to selectively kill cancer cells under a moderate alternating magnetic field (44 mT and 70 kHz).

Control of crystallite orientation and size in Fe and FeCo nanoneedles.

Uniform magnetic nanoneedles have been prepared by hydrogen reduction of elongated nanoarchitectures. These precursors are as-prepared or cobalt-coated aggregates of highly oriented haematite nanocrystals (∼5 nm). The final materials are flattened nanoneedles formed by chains of assembled Fe or FeCo single-domain nanocrystals. The microstructural properties of such nanoneedles were tailored using renewed and improved synthetic strategies. In this fashion, the needle elongation and composition, the crystallite size (from 15 up to 30 nm), the nanocrystal orientation (with the 〈110〉 or 〈001〉 directions roughly along the long axis of the nanoneedle) and their type of arrangement (single chains, frustrated double chains and double chains) were controlled by modifying the reduction time, the axial ratio of the precursor haematite and the presence of additional coatings of aluminum or yttrium compounds. The values of the coercivity H(C) found for these nanoneedles are compared with the values predicted by the chain of spheres model assuming a symmetric fanning mechanism for magnetization reversal.

Dimercaptosuccinic acid-coated magnetite nanoparticles for magnetically guided in vivo delivery of interferon gamma for cancer immunotherapy.

As radio- and chemotherapy-based cancer treatments affect both tumors and healthy tissue, cancer immunotherapy attempts to specifically enhance the natural immune response to tumor cells. In mouse models of cancer, we tested uniform dimercaptosuccinic acid (DMSA)-coated monodisperse magnetic nanoparticles as a delivery system for the anti-tumorigenic cytokine IFN-γ. IFN-γ-adsorbed DMSA-coated magnetic nanoparticles were targeted to the tumor site by application of an external magnetic field. We analyzed nanoparticle biodistribution before and after IFN-γ conjugation, as well as the efficiency of nanoparticle accumulation in tumors, IFN-γ release in the area of interest, and the effects of both on tumor development. At the tumor site, we observed a high degree of nanoparticle accumulation and of cytokine delivery, which led to increased T cell and macrophage infiltration and promoted an anti-angiogenic effect. The combined action led to a notable reduction in tumor size. Our findings indicate that IFN-γ-adsorbed DMSA-coated magnetite nanoparticles can be used as an efficient in vivo drug delivery system for tumor immunotherapy.

The endocytic penetration mechanism of iron oxide magnetic nanoparticles with positively charged cover: a morphological approach.

In this study we present a morphological approach in observing the interaction of cationic magnetic nanoparticles with A-549 cells (human lung adenocarcinoma). Under our experimental conditions, nanoparticles easily penetrated cells and were observed in vivo, using bright light microscopy. In fixed cells, nanoparticles remained inside cells, showing quantity and distribution patterns similar to those in unfixed cells. The presence of nanoparticles did not affect cell viability or the morphologic parameters assessed. We determined the potential internalization mechanism of nanoparticles into cells using endocytosis inhibitors. The results suggest that nanoparticles used in this study penetrate A-549 cells mainly through a macropinocytosis process.

Liver and brain imaging through dimercaptosuccinic acid-coated iron oxide nanoparticles.

BACKGROUND & AIM: Uptake, cytotoxicity and interaction of improved superparamagnetic iron oxide nanoparticles were studied in cells, tissues and organs after single and multiple exposures. MATERIAL & METHOD: We prepared dimercaptosuccinic acid-coated iron oxide nanoparticles by thermal decomposition in organic medium, resulting in aqueous suspensions with a small hydrodynamic size (< 100 nm), high saturation magnetization and susceptibility, high nuclear magnetic resonance contrast and low cytotoxicity. RESULTS: In vitro and in vivo behavior showed that these nanoparticles are efficient carriers for drug delivery to the liver and brain that can be combined with MRI detection.

Ordered ferrimagnetic form of ferrihydrite reveals links among structure, composition, and magnetism.

The natural nanomineral ferrihydrite is an important component of many environmental and soil systems and has been implicated as the inorganic core of ferritin in biological systems. Knowledge of its basic structure, composition, and extent of structural disorder is essential for understanding its reactivity, stability, and magnetic behavior, as well as changes in these properties during aging. Here we investigate compositional, structural, and magnetic changes that occur upon aging of "2-line" ferrihydrite in the presence of adsorbed citrate at elevated temperature. Whereas aging under these conditions ultimately results in the formation of hematite, analysis of the atomic pair distribution function and complementary physicochemical and magnetic data indicate formation of an intermediate ferrihydrite phase of larger particle size with few defects, more structural relaxation and electron spin ordering, and pronounced ferrimagnetism relative to its disordered ferrihydrite precursor. Our results represent an important conceptual advance in understanding the nature of structural disorder in ferrihydrite and its relation to the magnetic structure and also serve to validate a controversial, recently proposed structural model for this phase. In addition, the pathway we identify for forming ferrimagnetic ferrihydrite potentially explains the magnetic enhancement that typically precedes formation of hematite in aerobic soil and weathering environments. Such magnetic enhancement has been attributed to the formation of poorly understood, nano-sized ferrimagnets from a ferrihydrite precursor. Whereas elevated temperatures drive the transformation on timescales feasible for laboratory studies, our results also suggest that ferrimagnetic ferrihydrite could form naturally at ambient temperature given sufficient time.

The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells.

The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was detected in cells incubated with neutral charged nanoparticles, while negative particles showed different behaviour depending on the nature of the coating. Thus, dimercaptosuccinic-coated nanoparticles showed low cellular uptake with non-toxic effects, while heparin-coated particles showed cellular uptake only at high nanoparticle concentrations and induced abnormal mitotic spindle configurations. Finally, cationic magnetic nanoparticles show excellent properties for possible in vivo biomedical applications such as cell tracking by magnetic resonance imaging (MRI) and cancer treatment by hyperthermia: (i) they enter into cells with high effectiveness, and are localized in endosomes; (ii) they can be easily detected inside cells by optical microscopy, (iii) they are retained for relatively long periods of time, and (iv) they do not induce any cytotoxicity.

Effect of nanoparticle and aggregate size on the relaxometric properties of MR contrast agents based on high quality magnetite nanoparticles.

Colloidal dispersions of monodispersed and high-crystalline magnetite nanoparticles have been used to establish a relationship between magnetic properties and magnetic resonance (MR) relaxometric parameters in vitro. Magnetite nanoparticles with diameters between 4 and 14 nm were synthesized by thermal decomposition of Fe(acac)3 in different organic solvents and transformed to hydrophilic by changing oleic acid for dimercaptosuccinic acid (DMSA). A final treatment in alkaline water was critical to make the suspension stable at pH 7 with xi-potential values of -45 mV and hydrodynamic sizes as low as 50 nm. Samples showed superparamagnetic behavior at room temperature, which is an important parameter for biomedical applications. Susceptibility increased with both particle and aggregate size, and for particles larger than 9 nm, the aggregate size was the key factor controlling the susceptibility. Relaxivity values followed the same trend as the suspension susceptibilities, indicating that the aggregate size is an important factor above a certain particle size governing the proton relaxation times. The highest relaxivity value, r2=317 s(-1) mM(-1), much higher than those for commercial contrast agents with similar hydrodynamic size, was obtained for a suspension consisting of 9 nm particles and 70 nm of hydrodynamic size, and it was assigned to the higher particle crystallinity in comparison to particles prepared by coprecipitation. Therefore, it can be concluded that in addition to the sample crystallinity, both particle size and aggregate size should be considered in order to explain the magnetic and relaxivity values of a suspension.

Cytokine adsorption/release on uniform magnetic nanoparticles for localized drug delivery.

Attachment of cytokines to magnetic nanoparticles has been developed as a system for controlled local drug release in cancer therapy. We studied the adsorption/release of murine interferon gamma (IFN-gamma) on negatively charged magnetic nanoparticles prepared by three different methods, including coprecipitation, decomposition in organic media, and laser pyrolysis. To facilitate IFN-gamma adsorption, magnetic nanoparticles were surface modified by distinct molecules to achieve high negative charge at pH 7, maintaining small aggregate size and stability in biological media. We analyzed carboxylate-based coatings and studied the colloidal properties of the resulting dispersions. Finally, we incubated the magnetic dispersions with IFN-gamma and determined optimal conditions for protein adsorption onto the particles, as well as the release capacity at different pH and as a function of time. Particles prepared by decomposition in organic media and further modified with dimercaptosuccinic acid showed the most efficient adsorption/release capacity. IFN-gamma adsorbed on these nanoparticles would allow concentration of this protein or other biomolecules at specific sites for treatment of cancer or other diseases.

Direct aerosol synthesis of carboxy-functionalized iron oxide colloids displaying reversible magnetic behavior.

A simple and rapid synthetic strategy for fabricating carboxy-functionalized iron oxide colloidal particles displaying reversible magnetic behavior is reported. The method is based on the pyrolysis of aerosols generated from ethanol/water solutions containing iron inorganic salts and mono- or polysaccharides. Essential to the success of the method are the use of hybrid (organo-inorganic) aerosols and the temperature of pyrolysis. The resulting material could be used in advanced biotechnological applications such as the magnetically assisted chemical separation of biocompounds.

Spherical iron/silica nanocomposites from core-shell particles.

A simple procedure to coat silica spheres with smooth layers of iron compounds is reported. It is based on the forced hydrolysis (60-85 degrees C) of iron(III) acetylacetonate solutions containing the silica cores and sodium dodecylsulfate (SDS). The role that the iron(III) precursor and SDS play in the formation of uniform coatings is discussed. The thermal evolution of the composites up to the crystallization of the initially amorphous coating was also studied. Finally, the core-shell particles, as prepared, were thermally reduced under hydrogen atmosphere to produce magnetic composites whose magnetic properties were also evaluated as a function of the reduction temperature.

Synthesis of monodisperse superparamagnetic Fe/silica nanospherical composites.

A new method for the synthesis of monodisperse superparamagnetic nanospherical composites with a core containing metallic alpha-Fe nanocrystals dispersed in a silica matrix, and a shell only containing silica, is reported. Essential to the formation of this microstructure is to work with lamellar-like structures in conditions close to the upper-phase boundary limit for formation of microemulsions, and to control the solubility and pH of the metallic precursors. An advantage of the method is its versatility, which allows us to change the particle size (both for the nanomagnets and for the composite) and the spatial arrangement of the nanomagnets in the matrix. Our results indicate that this material could be adequate for biotechnology applications.

Uniform nanosized goethite particles obtained by aerial oxidation in the FeSO4-Na2CO3 system.

Pure goethite particles in the nanometer size range (from approximately 200 to approximately 80 nm) with an elongated shape (axial ratio from approximately 5 to approximately 8) useful as iron precursors for magnetic recording have been prepared by oxidation of the suspensions resulting from the addition of sodium carbonate to Fe(II) sulfate aqueous solutions under a restrictive set of experimental conditions (Fe(II) concentration, carbonate/Fe(II) mole ratio, temperature, and air flow rate). In all cases, the goethite particles were formed by a dissolution-recrystallization mechanism through an intermediate green-rust phase. The particle size was determined by the carbonate/Fe(II) ratio (which controls the formation pH), the FeSO(4) concentration, and the air flow rate. The smallest particles (length 80 nm) were obtained for a high carbonate/Fe(II) mole ratio (>/=3), a low Fe(II) concentration (0.075 mol dm(-3)), and an air flow rate of 2 dm(3) min(-1). The goethite particles were also characterized by the electron diffraction and high-resolution TEM finding that they were monocrystalline, having the crystalline c axis parallel to the longest particle dimension.