ABSTRACT: Finally, we have addressed some relevant findings on the importance of having well-defined synthetic strategies developed for the generation of MNPs, with a focus on particle formation mechanism and recent modifications made on the preparation of monodisperse samples of relatively large quantities not only with similar physical features, but also with similar crystallochemical characteristics. Then, different methodologies for the functionalization of the prepared MNPs together with the characterization techniques are explained. Theorical views on the magnetism of nanoparticles are considered.

Functionalization of iron oxide nanoparticles with quaternary ammonium ion-based aminooxy and oxime ether substrates provides a flexible route for generating magnetic gene delivery vectors. Using the MCF-7 breast cancer cell line, our findings show that pDNA magnetoplexes derived from the lipid-coated nanoparticle formulation dMLP transfect in the presence of 10% serum with or without magnetic assistance at significantly higher levels than a commonly used cationic liposome formulation, based on luciferase assay. The present ion-pairing, click chemistry approach furnishes Fe(3)O(4) nanoparticles with lipid layers. The resultant magnetic nanovectors serve as transfection enhancers for otherwise transfection-inactive materials.

Gold nanoshell around super paramagnetic iron oxide nanoparticles (SPIONs) was synthesized and small angle X-ray scattering (SAXS) analysis suggests a gold coating of approximately 0.4 to 0.5 nm thickness. On application of low frequency oscillating magnetic fields (44 - 430 Hz), a four- to five-fold increase in the amount of heat released with gold-coated SPIONs (6.3 nm size) in comparison with SPIONs (5.4 nm size) was observed. Details of the influence of frequencies of oscillating magnetic field, concentration and solvent on heat generation are presented. We also show that, in the absence of oscillating magnetic field, both SPIONs and SPIONs@Au are not particularly cytotoxic to mammalian cells (MCF-7 breast carcinoma cells and H9c2 cardiomyoblasts) in culture, as indicated by the reduction of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium by viable cells in a phenazine methosulfate-assisted reaction.

This study intended to prepare iron oxide nanoparticle-entrapped chitosan (CS) nanoparticles for stem cell labeling. The nanoparticles were synthesized by polymerizing iron oxide nanoparticle-associated methacrylic acid monomer in the presence of CS. TEM revealed that the well-defined iron oxide nanoparticles were successfully encapsulated inside the CS nanoparticles. The effect of CS at different [NH(2)]/[COOH] molar ratios on particle size, surface charge, thermal stability and magnetic properties was determined systematically. Internalization and localization of the coated nanoparticles were evaluated by atomic absorption spectrometry and confocal laser scanning microscopy. The Kusa O cell line was chosen as a stem cell model. Interestingly, the uptake of iron oxide-entrapped CS nanoparticles was remarkably enhanced under magnetization and the nanoparticles were mostly located inside cellular compartments. It can be concluded that the iron oxide-entrapped CS nanoparticles have a strong potential for stem cell labeling.

In this study, superparamagnetic monodisperse magnetite colloids, around 5nm in size, were prepared by dissolving iron chlorides, sodium hydroxide (NaOH) and sodium oleate (NaOL), in toluene/ethanol/water mixtures and refluxing for 4h. The concentrations of NaOH and NaOL were varied to systematically investigate the effect on the surface properties, size, dispersion, and magnetic properties of magnetite nanoparticles (MNPs). The samples were characterized via XRD, FTIR, TGA, TEM, SAED, DLS, and VSM. The results indicated that the surface coatings of MNPs could be manipulated from oleate to hydroxyl groups via increasing the molar ratio of NaOH/Fe(II) more than 8. The amount of NaOH had no obvious influence on the size and the saturation magnetization of MNPs. Therefore NaOH was not a necessary reactant for forming magnetite crystals. On the contrary, NaOL was shown to be the most important component for synthesizing stable magnetite colloids. The NaOL acted as both a key reactant to buffer the pH environment and a surfactant to keep the MNPs stable in nonpolar solvent media.

In a magnetofection procedure, self-assembling complexes of enhancers like cationic lipids with plasmid DNA or small interfering RNA (siRNA) are associated with magnetic nanoparticles and are then concentrated at the surface of cultured cells by applying a permanent inhomogeneous magnetic field. This process results in a considerable improvement in transfection efficiency compared to transfection carried out with nonmagnetic gene vectors. This article describes how to synthesize magnetic nanoparticles suitable for nucleic acid delivery by liposomal magnetofection and how to test the plasmid DNA and siRNA association with the magnetic components of the transfection complex. Protocols are provided for preparing magnetic lipoplexes, performing magnetofection in adherent and suspension cells, estimating the association/internalization of vectors with cells, performing reporter gene analysis, and assessing cell viability. The methods described here can be used to screen magnetic nanoparticles and formulations for the delivery of nucleic acids by liposomal magnetofection in any cell type.

Advances in nanotechnology have pushed forward the synthesis of a variety of functional nanoparticles (NPs) such as semiconductor quantum dots (QDs), magnetic and metallic NPs. The unique electronic, magnetic, and optical properties exhibited by these nanometer-sized materials have enabled a broad spectrum of biomedical applications. In particular, iron-oxide-based magnetic NPs have proved to be highly versatile deep-tissue imaging agents, having been incorporated into clinical applications due to their biocompatibility. This Interdisciplinary Review will focus on the recent advances in strategies for the synthesis and surface modification of highly monodisperse magnetic NPs and their use in imaging, drug delivery, and innovative ultrasensitive bioassays.

Superparamagnetic iron oxide nanoparticles can be used for numerous applications such as MRI contrast enhancement, hyperthermia, detoxification of biological fluids, drug delivery, or cell separation. In this work, we will summarize the chemical routes for synthesis of iron oxide nanoparticles, the fluid stabilization, and the surface modification of superparamagnetic iron oxide nanoparticles. Some examples of the numerous applications of these particles in the biomedical field mainly as MRI negative contrast agents for tissue-specific imaging, cellular labeling, and molecular imaging will be given. Larger particles or particles displaying a non-neutral surface (thanks to their coating or to a cell transfection agent with which they are mixed) are very useful tools, although the cells to be labeled have no professional phagocytic function. Labeled cells can then be transplanted and monitored by MRI in a broad spectrum of applications. Direct in vivo magnetic labeling of cells is mainly performed by intravenous injection of long-circulating iron oxide-based MRI contrast agents, which can extravasate and/or undergo a cellular uptake in an amount sufficient to allow an MRI visualization of areas of interest such as inflamed regions or tumors. Particles with long circulation times, or able to induce a strong negative effect individually have been also modified by conjugation to a ligand, so that their cellular uptake, or at least their binding to the cell surface, could occur through a specific ligand-receptor interaction, in vivo as well as in vitro. Thus, experimentally as well as in a few trials on humans, iron oxide particles currently find promising applications.

The grafting of pegylated dendrons on 9(2) nm and 39(5) nm iron oxide nanoparticles in water, through a phosphonate group as coupling agent has been successfully achieved and its mechanism investigated, with a view to produce biocompatible magnetic nano-objects for biomedical applications. Grafting has been demonstrated to occur by interaction of negatively charged phosphonate groups with positively charged groups and hydroxyl at the iron oxide surface. The isoelectric point of the suspension of dendronized iron oxide nanoparticles is shifted towards lower pH as the amount of dendron increases. It reaches 4.7 for the higher grafting rate and for both particle size. Thus, the grafting of molecules using a phosphonate group allows stabilizing electrostatically the suspensions at physiological pH, a prerequisite for biomedical applications. Moreover the grafting step has been shown to preserve the magnetic properties of iron oxide nanoparticles due to super-super exchange interactions through the phosphonate group.

A novel method for control burst releasing of drug via a high frequency magnetic field (HFMF) from magnetic-sensitive silica nanospheres was developed. The nanospheres were synthesized by a combination of emulsion and sol-gel process with the particles controlled at about 80 nm in diameter. Under repeated exposures to the high frequency magnetic stimulus, the drug release behaviors showed reproducible slow-to-burst profiles while consecutively applying the magnetic stimulus at 10-min switching time and the release profile restored immediately when the stimulus was removed. By taking this non-contact control-burst method, the magnetic silica nanospheres can be designed to treat the cancer therapy and urgent physiological needs.

The emulsion droplet solvent evaporation method has been used to prepare nanoclusters of monodisperse magnetite nanoparticles of varying morphologies depending on the temperature and rate of solvent evaporation and on the composition (solvent, presence of polymer, nanoparticle concentration, etc.) of the emulsion droplets. In the absence of a polymer, and with increasing solvent evaporation temperatures, the nanoparticles formed single- or multidomain crystalline superlattices, amorphous spherical aggregates, or toroidal clusters, as determined by the energetics and dynamics of the solvent evaporation process. When polymers that are incompatible with the nanoparticle coatings were included in the emulsion formulation, monolayer- and multilayer-coated polymer beads and partially coated Janus beads were prepared; the nanoparticles were expelled by the polymer as its concentration increased on evaporation of the solvent and accumulated on the surfaces of the beads in a well-ordered structure. The precise number of nanoparticle layers depended on the polymer/magnetic nanoparticle ratio in the oil droplet phase parent emulsion. The magnetic nanoparticle superstructures responded to the application of a modest magnetic field by forming regular chains with alignment of nonuniform structures (e.g., toroids and Janus beads) that are in accord with theoretical predictions and with observations in other systems.

Water-dispersible Fe(3)O(4) nanoparticles have been prepared by a simple solution method, in which the particle size (3-11 nm) can be tuned by simply adjusting the reaction temperature and time; the formation mechanism of Fe(3)O(4) nanoparticles is proposed and their low cytotoxicity has also been proved.

Superparamagnetic iron oxide nanoparticles (SPIONs) have attract a great deal of interest in biomedical research and clinical applications over the past decades. Taking advantage the fact that SPIONs only exhibit magnetic properties in the presence of an applied magnetic field, they have been used in both in vitro magnetic separation and in vivo applications such as hyperthermia (HT), magnetic drug targeting (MDT), magnetic resonance imaging (MRI), gene delivery (GD) and nanomedicine. Successful applications of SPIONs rely on precise control of the particle's shape, size, and size distribution and several synthetic routes for preparing SPIONs have been explored. Tailored surface properties specifically designed for cell targeting are often required, although the generic strategy involves creating biocompatible polymeric or non-polymeric coating and subsequent conjugation of bioactive molecules. In this review article, synthetic routes, surface modification and functionaliztion of SPIONs, as well as the major biomedical applications are summarized, with emphasis on in vivo applications.

Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.

In this study, a magnetic-sensitive microcapsule was prepared using Fe 3O 4/poly(allylamine)(Fe 3O 4/PAH) polyelectrolyte to construct the shell. Structural integrity, microstructural evolution, and corresponding release behaviors of fluorescence dyes and doxorubicin were systematically investigated. Experimental observations showed that the presence of the magnetic nanoparticles in the shell structure allowed the shell structure to evolve from nanocavity development to final rupture of the shell under a given magnetic stimulus of different time durations. Such a microstructural evolution of the magnetic sensitive shell structure explained a corresponding variation of the drug release profile, from relatively slow release to burst-like behavior at different stages of stimulus. It has proposed that the presence of magnetic nanoparticles produced heat, due to magnetic energy dissipation (as Brown and Neel relaxations), and mechanical vibration and motion that induced stress development in the thin shell. Both mechanisms significantly accelerated the relaxation of the shell structure, causing such a microstructural evolution. With such a controllable microstructural evolution of the magnetic-sensitive shell structure, active substances can be well-regulated in a manageable manner with a designable profile according to the time duration under magnetic field. A cell culture study also indicated that the magnetic-sensitive microcapsules allowed a rapid uptake by the A549 cell line, a cancerous cell line, suggesting that the magnetic-sensitive microcapsule with controllable rupturing behavior of the shell offers a potential and effective drug carrier for anticancer applications.

Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to specifically tailor the features and properties of MNPs for these biomedical applications. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. Through the incorporation of highly specific targeting agents and other functional ligands, such as fluorophores and permeation enhancers, the applicability and efficacy of these MNPs have greatly increased. This review provides a background on applications of MNPs as MR imaging contrast agents and as carriers for drug delivery and an overview of the recent developments in this area of research.

Water-soluble monodisperse superparamagnetic Fe(3)O(4) nanocrystals decorated with two distinct functional groups are prepared in a single-step procedure by injecting iron precursors into a refluxing aqueous solution of a polymer ligand, trithiol-terminated poly(methacrylic acid)(PMAA-PTTM), bearing both carboxylate and thiol functionalities. The ratio of carboxylic acid groups in the polymer-protecting ligand to the iron precursors plays a key role in determining the particle size and particle size distribution. The surface functionalities of the ligands allow post-synthesis modification of the materials to produce water-soluble fluorescent magnetic nanocrystals.

This protocol details how to design and conduct experiments to deliver nucleic acids to adherent and suspension cell cultures in vitro by magnetic force-assisted transfection using self-assembled complexes of nucleic acids and cationic lipids or polymers (nonviral gene vectors), which are associated with magnetic (nano) particles. These magnetic complexes are sedimented onto the surface of the cells to be transfected within minutes by the application of a magnetic gradient field. As the diffusion barrier to nucleic acid delivery is overcome, the full vector dose is targeted to the cell surface and transfection is synchronized. In this manner, the transfection process is accelerated and transfection efficiencies can be improved up to several 1,000-fold compared with transfections carried out with nonmagnetic gene vectors. This protocol describes how to accomplish the following stages: synthesis of magnetic nanoparticles for magnetofection; testing the association of DNA with the magnetic components of the transfection complex; preparation of magnetic lipoplexes and polyplexes; magnetofection; and data processing. The synthesis and characterization of magnetic nanoparticles can be accomplished within 3-5 d. Cell culture and transfection is then estimated to take 3 d. Transfected gene expression analysis, cell viability assays and calibration will probably take a few hours. This protocol can be used for cells that are difficult to transfect, such as primary cells, and may also be applied to viral nucleic acid delivery. With only minor alterations, this protocol can also be useful for magnetic cell labeling for cell tracking studies and, as it is, will be useful for screening vector compositions and novel magnetic nanoparticle preparations for optimized transfection efficiency in any cell type.

We report the fabrication and characterization of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and their application to the dual imaging of cancer in vivo. Unlike dextran-coated cross-linked iron oxide nanoparticles, which are prepared by a chemical cross-linking method, TCL-SPION are prepared by a simple, thermal cross-linking method using a Si-OH-containing copolymer. The copolymer, poly(3-(trimethoxysilyl)propyl methacrylate-r-PEG methyl ether methacrylate-r-N-acryloxysuccinimide), was synthesized by radical polymerization and used as a coating material for as-synthesized magnetite (Fe3O4) SPION. The polymer-coated SPION was further heated at 80 degrees C to induce cross-linking between the -Si(OH)3 groups in the polymer chains, which finally generated TCL-SPION bearing a carboxyl group as a surface functional group. The particle size, surface charge, presence of polymer-coating layers, and the extent of thermal cross-linking were characterized and confirmed by various measurements, including dynamic light scattering, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The carboxyl TCL-SPION was converted to amine-modified TCL-SPION and then finally to Cy5.5 dye-conjugated TCL-SPION for use in dual (magnetic resonance/optical) in vivo cancer imaging. When the Cy5.5 TCL-SPION was administered to Lewis lung carcinoma tumor allograft mice by intravenous injection, the tumor was unambiguously detected in T2-weighted magnetic resonance images as a 68% signal drop as well as in optical fluorescence images within 4 h, indicating a high level of accumulation of the nanomagnets within the tumor site. In addition, ex vivo fluorescence images of the harvested tumor and other major organs further confirmed the highest accumulation of the Cy5.5 TCL-SPION within the tumor. It is noteworthy that, despite the fact that TCL-SPION does not bear any targeting ligands on its surface, it was highly effective for tumor detection in vivo by dual imaging.

Monodispersed, spherical gamma-Fe2O3 nanoparticles with controllable size in large-scale were prepared by thermolytic decomposition of FeCl3.6H2O in aliphatic amines. The nanoparticles gave very stable colloidal solution in organic solvents and can be easily converted to water-soluble by a very simple route. Their characterisation was based on TEM microscopy, XRD, Mössbauer, and magnetic measurements. Furthermore, a small amount of Pt can lead to the formation of anisotropic gamma-Fe2O3 nanostructures.