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PubMed2006

Synthesis of biocompatible poly[2-(methacryloyloxy)ethyl phosphorylcholine]-coated magnetite nanoparticles.

A well-defined, double-hydrophilic diblock copolymer comprising poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-(glycerol monomethacrylate) (PMPC30-PGMA30, where the numbers represent the average degrees of polymerization for each block) was evaluated for the synthesis of colloidally stable ultrafine magnetite sols. Sterically stabilized paramagnetic sols were prepared in aqueous solution by chemical coprecipitation of ferric and ferrous salts in the presence of this block copolymer. The PMPC30-PGMA30-stabilized magnetite sol had a mean transmission electron microscopy (TEM) diameter of 9.4 +/- 1.7 nm and a mean hydrodynamic diameter of 34 nm. This sol exhibited improved colloidal stability with respect to long-term storage and pH variation compared with magnetite sols prepared in the presence of alternative water-soluble homopolymers and diblock copolymers. Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry, electron spectroscopy imaging (ESI), and zeta potential studies indicate that the PMPC30-PGMA30 diblock copolymer was adsorbed onto the surface of the sol via the PGMA30 block, with the PMPC30 chains acting as the stabilizing block. Such sterically stabilized sols are expected to be improved contrast agents for magnetic resonance imaging (MRI) applications.

Coated Materials, Biocompatible↗
PubMed2007

Construction of multi-layered cardiomyocyte sheets using magnetite nanoparticles and magnetic force.

Heart tissue engineering requires construction of three-dimensional (3-D) tissues composed of cardiomyocytes (CMs) that are tightly connected to each other. The aim of this study was to construct "scaffold-less" multi-layered 3-D CM sheets using magnetic force-based tissue engineering (Mag-TE) and to evaluate the cell-to-cell functional connections within the CM sheets. Original magnetite cationic liposomes (MCLs) with a positive surface charge (which facilitate adsorption to the target cell surface) were taken up by CMs that were isolated from 2-day-old Wistar rats. When MCLs were added to the medium of CMs at magnetite concentrations of 25, 50, and 100 pg per cell, subsequent measurements showed that 7.2, 13.2, and 27.3 pg of magnetite were taken up per cell, respectively, after 4 h incubation at 37 degrees C. Further, no toxicity was observed after a 24 h incubation period. Using magnetically labeled CMs (magnetite concentration, 100 pg/cell), multi-layered CM sheets were constructed. Immunofluorescent staining of connexin43 demonstrated the presence of gap junctions within the CM sheets that were constructed by Mag-TE. Moreover, electrical connections within the CM sheets constructed by Mag-TE were confirmed using extracellular potential mapping. These results indicate that Mag-TE is a viable methodology for heart tissue engineering.

Animals↗
PubMed2003

Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles.

In this study we demonstrated that heat shock protein (HSP) 70 expression by hyperthermia induced antitumor immunity in the T-9 rat glioma. Our hyperthermic system using magnetic nanoparticles induced necrotic cell death that correlated with HSP70 expression. We purified the HSP70-peptide complexes from the tumor after hyperthermia to investigate whether HSP70 was involved in the antitumor immunity, and we found that in the F344 rats immunized with T-9-derived HSP70 the tumor growth of T-9 was significantly suppressed. Tumor rejection assay after hyperthermic treatment of implanted T-9 cells with incorporated magnetite cationic liposomes (MCL) was performed to investigate whether antitumor immunity was induced by release of HSP70 from the necrotic cells in the F344 rat. Tumor growth was strongly suppressed in the rats subjected to hyperthermia of implanted T-9 cells, and 50% of rats were protected from challenge with T-9 cells. Immunogenicity was enhanced when the HSP70-overexpressing T-9 cells were killed via necrosis in rats by hyperthermia, after which all rats were completely protected from challenge with T-9 cells. Our hyperthermic system produces vaccination with HSP70-peptide via necrotic tumor cell death in vivo, resulting in antitumor immunity. This phenomenon, which may be termed in situ vaccination, has important implications for the development of novel antitumor therapies.

Animals↗
PubMed2004

Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy.

In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with 188Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl2 x 2H2O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 microl and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study.

Adsorption↗
PubMed2005

Magnetite nanoparticles with tunable gold or silver shell.

Fe3O4 nanoparticles with size approximately 13 nm have been prepared successfully in aqueous micellar medium at approximately 80 degrees C. To make Fe3O4 nanoparticles resistant to surface poisoning a new route is developed for coating Fe3O4 nanoparticles with noble metals such as gold or silver as shell. The shell thickness of the core-shell particles becomes tunable through the adjustment of the ratio of the constituents. Thus, the route yields well-defined core-shell structures of size from 18 to 30 nm with varying proportion of Fe3O4 to the noble metal precursor salts. These magnetic nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), FTIR, differential scanning calorimetry (DSC), Raman and temperature-dependent magnetic studies.

Journal Article↗
PubMedDate not supplied

Antibody-magnetite nanoparticles: in vitro characterization of a potential tumor-specific contrast agent for magnetic resonance imaging.

Target-specific superparamagnetic contrast agents may allow the localization of specific tissues such as tumors by magnetic resonance imaging (MRI). In this report the preparation and in vitro characterization of tumor-specific superparamagnetic particles (SMP) are described. Particles of uniform size (9.6 +/- 0.8 nm) were prepared from an alkaline solution of ferric and ferrous ions and isolated by differential centrifugation. The resulting nanoparticle suspension is stabilized in buffer using a polypeptide coat to which a monoclonal antibody, specific to carcinoembryonic antigen (CEA), was covalently attached at the hinge region. The resulting anti-CEA SMP have a hydrodynamic radius of less than 50 nm, and specifically bind to CEA in vitro. The visualization of epitopes, present on a cell surface in very low density as expected for tumor antigens or receptors, may be achieved due to the high R2 relaxivity of 300 L mmol-1s-1 of the contrast agent described here. Furthermore, the polypeptide coat chosen provides an ideal platform for the attachment of biological modifiers needed for the reduction of the antigenicity and blood clearance rate of anti-CEA SMP.

Antibodies↗
PubMed2006

A biocompatible method of decorporation: bisphosphonate-modified magnetite nanoparticles to remove uranyl ions from blood.

We report on the use of bisphosphonate to functionalize Fe3O4 magnetic nanoparticles via dopamine (DA) linkage. Using tetraethyl-3-aminopropane-1,1-bisphosphonate (BP) as the functional molecule, we created a system with an Fe3O4-DA-BP nanostructure, which possesses high specificity for removing uranyl ions from water or blood. This work demonstrates that magnetic nanoparticles, combined with specific receptor-ligand interactions, promise a sensitive and rapid platform for the detection, recovery, and decorporation of metal toxins from biological environment.

Biocompatible Materials↗
PubMed2004

Superparamagnetism of magnetite nanoparticles: dependence on surface modification.

Superparamagnetic iron oxide nanoparticles (SPION) with an average particle diameter of 6 nm are prepared by controlled chemical coprecipitations. Colloidal suspensions of noninteracting SPION, where the surface has been modified with three different types of biocompatible substances, namely, starch, gold (Au), and methoxypoly(ethylene glycol) (MPEG) have been fabricated via three different techniques. Starch-coated SPION are prepared by coprecipitation in a polymeric matrix, Au-coated SPION are fabricated by the microemulsion method, and MPEG-coated SPION are prepared using the self-assembly approach. The magnetic nanoparticles form a core-shell structure, and the magnetic dipole-dipole interactions are screened by a layer of coating agents. The amounts of coating agents and SPION are indirectly calculated from the thermogravimetric analysis and superconducting quantum interference device measurements by assuming passive oxidation on the surface of the SPION, and the other conditions do not influence the measurements. The dependency of the spectral characteristics of Mössbauer spectroscopy as a function of an external magnetic field Hext is measured to investigate the effect of dipole-dipole screening of the different coating layers on the SPION. Uncoated SPION show a stable magnetic moment under Hext, and the superparamagnetic (SPM) fraction transforms to a ferrimagnetic state. Starch and Au-coated SPION retain the SPM fraction according to Mössbauer spectroscopy and magnetization measurements. MPEG-coated SPION show hyperfine magnetic structure without the quadrupole effect with increasing the value of the blocking temperature.

Journal Article↗
PubMed2004

Self-assembled coatings on individual monodisperse magnetite nanoparticles for efficient intracellular uptake.

Monodispersed iron oxide superparamagnetic nanoparticles were prepared using a novel circulating system. A simple dialysis method was developed to immobilize nanoparticles with functional biopolymers and targeting agents, which avoids the use of the normal centrifugation process that may cause particle agglomeration during the coating process. To enhance the specific targeting capability of the nanoparticles, a new chemical scheme was introduced, in which folic acid (FA) was chosen as the targeting agent combined with PEG serving to improve biocompatibility of nanoparticles. The AFM characterization showed that the nanoparticles produced are well dispersed with a narrow size distribution. The FTIR and XPS spectrum analyses indicated that PEG and FA-PEG have been chemically/covalently bonded to nanoparticles using synthetic approach introduced in this study. Our biological study showed that coating nanoparticles with PEG-FA significantly enhanced the intracellular uptake of nanoparticles by target cells.

Adsorption↗
PubMed2005

Biodesulfurization of dibenzothiophene by microbial cells coated with magnetite nanoparticles.

Microbial cells of Pseudomonas delafieldii were coated with magnetic Fe3O4 nanoparticles and then immobilized by external application of a magnetic field. Magnetic Fe3O4 nanoparticles were synthesized by a coprecipitation method followed by modification with ammonium oleate. The surface-modified Fe3O4 nanoparticles were monodispersed in an aqueous solution and did not precipitate in over 18 months. Using transmission electron microscopy (TEM), the average size of the magnetic particles was found to be in the range from 10 to 15 nm. TEM cross section analysis of the cells showed further that the Fe3O4 nanoparticles were for the most part strongly absorbed by the surfaces of the cells and coated the cells. The coated cells had distinct superparamagnetic properties. The magnetization (delta(s)) was 8.39 emu.g(-1). The coated cells not only had the same desulfurizing activity as free cells but could also be reused more than five times. Compared to cells immobilized on Celite, the cells coated with Fe3O4 nanoparticles had greater desulfurizing activity and operational stability.

Bacterial Adhesion↗
PubMed2006

Citric-acid-coated magnetite nanoparticles for biological applications.

Water-based magnetic fluids, generally intended for biomedical applications, often have various coating molecules that make them stable and compatible with biological liquids. Magnetic fluids containing iron oxide particles have been prepared by a co-precipitation method, using citric acid as stabilizer. The magnetic particles of the magnetic fluids were obtained by chemical precipitation from ferric (FeCl(3)) and ferrous salts (FeSO(4) or FeCl(2)) in alkali medium (ammonia hydroxide). Citric acid was used to stabilize the magnetic-particle suspension. Physical tests were performed in order to determine various microstructural and rheological features. Transmission electron microscopy was the main investigation method for assessing the magnetic-particle size. The dimensional distribution of the magnetic-particle physical diameter was analyzed using the box-plot statistical method while infrared absorption spectra were used to study the colloidal particle structure. The magnetic-fluid density (picnometric method), viscosity (capillary method) and surface tension (stalagmometric method) were measured using standard methods.

Ammonium Hydroxide↗
PubMed2006

Growth and characterization of highly branched nanostructures of magnetic nanoparticles.

Magnetite nanoparticles of Fe(3)O(4) have been found to grow into large highly branched nanostructures including nanochains and highly branched nanotrees in the solid state through a postannealing process. By varying the preparation conditions such as annealing time and temperature, the nanostructures could be easily manipulated. Changing the starting concentration of the magnetic nanoparticle solution also caused significant changes of the nanoarchitectures. When the magnetic nanoparticle concentration is low, the nanoparticles formed straight rods mainly with an average diameter of 80 nm and a length of several microns. With increasing concentration of the nanoparticles, treelike structures began to form. With further increase of the concentration, well-ordered nanostructures with the appearance of snowflakes were generated. The driving force for the formation of the highly ordered nanostructures includes interaction between the nanoparticles and interaction through surface-capping molecules. This experiment demonstrates that novel nanostructures can be generated by self-assembly of magnetic nanoparticles under the solid state.

Chemistry, Physical↗
PubMed2005

Particle size and magnetic field-induced optical properties of magnetic fluid nanoparticles.

Magnetite nanoparticles with diameters of 7, 9, and 12 nm have been prepared by a chemical coprecipitation method. The transmission of light through magnetic fluid containing these nanoparticles has been investigated as a function of film thickness with wavelength between 400 and 750 nm, and applied magnetic fields up to 275 Oe. The transmission threshold shifts to the lower wavelength side with decreasing magnetic fluid film thickness as well as the particle size. For a given film thickness, the transmittance increases with increasing magnetic field for films with a particle size of 7 and 9 nm, but decreases in the 12-nm film. This is attributed to the competition between the van der Waals and dipole-dipole interaction.

Journal Article↗
PubMed1999

Physical and Chemical Properties of Magnetite and Magnetite-Polymer Nanoparticles and Their Colloidal Dispersions.

The properties of polymer-coated magnetite nanoparticles, which have the potential to be used as effective magnetic resonance contrast agents, have been studied. The magnetite particles were synthesized by using continuous synthesis in an aqueous solution. The polymer-coated magnetite nanoparticles were synthesized by seed precipitation polymerization of methacrylic acid and hydroxyethyl methacrylate in the presence of the magnetite nanoparticles. The particle size was measured by laser light scattering. It was shown that the particle size, variance, magnetic properties, and stability of aqueous magnetite colloidal dispersion strictly depend on the nature of the stabilizing agent. The average hydrodynamic radius of the magnetite particles was found to be 5.7 nm in the stable aqueous colloidal dispersion. An inclusion of the magnetite particle into a hydrophilic polymeric shell increases the stability of the dispersion and decreases the influence of the stabilizing agent on the magnetic and structural properties of the magnetite particles as was shown by X-ray diffraction and Mössbauer and IR spectroscopy, as well as by vibrating sample magnetometry. The variation in the polymeric shell size and the polymer net density can be useful tools for evaluation of the polymer-coated magnetite particles as effective contrast agents. Copyright 1999 Academic Press.

Journal Article↗
PubMed2004

Magnetite nanoparticle-loaded anti-HER2 immunoliposomes for combination of antibody therapy with hyperthermia.

Anti-HER2 antibody can induce antitumor responses, and can be used in delivering drugs to HER2-overexpressing cancer. Previously, we produced hyperthermia using magnetite nanoparticles that generate heat in an alternating magnetic field. In the present study, we constructed anti-HER2 immunoliposomes containing magnetite nanoparticles, which act as tumor-targeting vehicles, combining anti-HER2 antibody therapy with hyperthermia. The magnetite nanoparticle-loaded anti-HER2 immunoliposomes exerted HER2-mediated antiproliferative effects on SKBr3 breast cancer cells in vitro. Moreover, 60% of magnetite nanoparticles were incorporated into SKBr3, and the cells were then heated at 42.5 degrees C under an alternating magnetic field, resulting in strong cytotoxic effects. These results suggest that this novel therapeutic tool is applicable to treatment of HER2-overexpressing cancer.

Antibodies, Monoclonal↗
PubMed2006

Loading magnetic nanoparticles into sperm cells does not affect their functionality.

The spontaneous loading of magnetite nanoparticles into sperm cell was carried out by mixing an aqueous colloidal solution of Fe3O4-PVA with sperm cells (10(8) cells/ml) for 2 h at 37 degrees C suspended in glucose-free modified Tyrode solution. The penetration of the magnetite nanoparticles into the sperm cells was monitored by conventional analytical chemistry. We have demonstrated that the motility and the ability to undergo the acrosome reaction (i.e., the ability to fertilize the egg) were not affected by the presence of the magnetite nanoparticles.

Journal Article↗
PubMed1994

Biodegradation of magnetite dextran nanoparticles in the rat. A histologic and biophysical study.

BACKGROUND: Superparamagnetic iron oxide particles represent a new class of contrast agents that increase the detectability of hepatic and splenic tumors by magnetic resonance imaging (MRI). Magnetite dextran nanoparticles, a preparation with a small mean particle diameter in solution and null zêta potential present high safety margin and efficacy. The purpose of this investigation was to define the main steps of the metabolism of the iron oxide crystals. EXPERIMENTAL DESIGN: Rats were intravenously administered a single small dose of 59Fe-labeled MD3 (3 mg Fe/kg), and the biodistribution of 59Fe was investigated in the different organs from 2 hours to 25 days postinjection. Magnetic susceptibility studies were conducted in parallel to light microscopy and immunohistochemistry from day 1 to day 14 after administration. RESULTS: Most of the dose accumulated in the carcass (45%), liver (7%), and spleen (7%) in the first 2 hours. In the spleen, a continuously iron uptake was observed up to 48 hours (44%), then decreased to 25 days (22%). The splenic magnetic susceptibility dropped sharply during the first days and then more slightly until day 14. In the liver and blood, the 59Fe-level decreased at 24 hours and then increased until day 25 (11% and 27%, respectively). Histochemistry features essentially confirmed the radiotracer data and showed that iron oxide cores were accumulated into the Kupffer cells and the macrophages of the splenic marginal zone. With time, the number of the granules was decreased whereas the fine iron granules appeared in the cytoplasm. Immunopositive staining for ferritin was markedly increased in the liver hepatocytes to 3 days after injection, and in the splenic marginal zone macrophages to 14 days after injection. CONCLUSIONS: The data point to the early biodegradation of the iron oxide crystals. MD3 thus appear as an interesting biodegradable new contrast agent first devoted to magnetic resonance imaging of liver and spleen diseases that could be further extended to heart, kidneys, and other organs.

Animals↗