Dextran Magnetite Research Articles

Dual-energy CT imaging of atherosclerotic plaque using novel ultrasmall superparamagnetic iron oxide in hyperlipidemic rabbits.

A study using magnetic resonance imaging (MRI) revealed that ultra-small superparamagnetic iron oxide is phagocytosed by macrophages. However, MRI has limitations in obtaining clear images due to its poor spatial and temporal resolutions. To examine whether the use of dual-energy computed tomography (DECT) facilitated the visualization of carboxymethyl-diethylaminoethyl dextran magnetite ultra-small superparamagnetic iron oxide (CMEADM-U) accumulation in arteriosclerotic lesions using hyperlipidemic rabbits. CMEADM-U at 0.5 mmol Fe/kg was administered to Watanabe hereditary atherosclerotic (WHHL) rabbits (n = 6, 24 sections) and New Zealand white (NZW) rabbits (n = 2, 6 sections). After 72 h, DECT was performed to prepare virtual monochromatic images (35 keV, 70 keV) and an iron-based map. Subsequently, the aorta was collected along with hematoxylin and eosin staining, Berlin blue (BB) staining, and RAM11 immunostaining. In the WHHL rabbits, CMEADM-U accumulation was not observed at 70 keV. However, CMEADM-U accumulation consistent with an arteriosclerotic lesion was observed at 35 keV and the iron-based map. On the other hand, in the NZW rabbits, there was no accumulation of CMEADM-U in any images. Further, there were significant differences in the iron-based map value at the site of accumulation among the grades of expression on BB staining and RAM11 immunostaining. In addition, there was a good correlation at 35 kev and iron-based map value (r = 0.42; P < 0.05). DECT imaging for CMEADM-U facilitated the assessment of macrophage accumulation in atherosclerotic lesions in an in vivo study using a rabbit model of induced aortic atherosclerosis.

Assessment of pulmonary mucociliary transport using magnetic nanoparticles: influence of their surface potential

Objective(s): Inhaled aerocontaminants are removed from the lungs by pulmonary mucociliary transport (MCT) as an important defense mechanism. This study was undertaken to investigate the influence of the surface potential of magnetic nanoparticles (MNPs) on the MCT in murine lungs by use of magnetic particle imaging (MPI).Materials and Methods: Three kinds of MNPs (carboxymethyl dextran magnetite (CM), alkali-treated dextran magnetite (AM), and trimethylammonium dextran magnetite (TM)) with almost the same hydrodynamic diameters (50-55 nm) but different surface (zeta) potentials (−24 mV for CM, −15 mV for AM, and +2 mV for TM) were intratracheally injected to anesthetized ICR male mice at 10 weeks old using a nebulizing microsprayer containing 50 μL of MNPs. MPI images were acquired at 0.5, 6, 24, 72, and 168 hours after the injection of agents for each mouse. The retention value of the MNPs in the lungs was quantified from the average pixel value of the lungs in the MPI image. Results: The retention value of TM in the lungs was significantly greater than that of AM at 6 and 168 hours after the injection of agents, and was significantly greater than that of CM at 72 and 168 hours after injection. The retention value of AM was significantly greater than that of CM at 168 hours after injection.Conclusion: The surface potential of MNPs affects the clearance of MNPs from the lungs due to MCT, suggesting that the retention of MNPs in the lungs can be controlled by manipulating the surface potential of MNPs. MPI will be useful for the visual and quantitative assessment of MCT, because MPI allows for repeated and long-term studies with a single injection of MNPs and with no radiation exposure.

Dextran coated superparamagnetic iron oxide nanoparticles produced by microfluidic process

Abstract Dextran coated biocompatible water-based magnetite (Fe3O4) nanostructured media was produced via microfluidic process at various flow rates. The influences of dextran molecular weight on the magnetite particle size and magnetic property of nano fluid were investigated. Magnetite produced at flow rate of 0.04 mL/s showed uniform particle size distribution with average size 10 nm and saturation magnetization (Ms) up to 60 emu/g. The X-ray diffraction pattern indicates pure phase of Fe3O4 as-synthesized nanoparticles with high crystallinity. Zero Field Cooled and Field Cooled measurements indicated a superparamagnetic nature of as synthesized particles with a low blocking temperature that varies by the amount of dextran introduced in the mixture. The Specific Power Absorption (SPA) value obtained of up to 130 W/g shows that the magnetite–dextran nanostructured fluid appears to be a promising active media for the local magnetic hyperthermia for cancer therapy.

A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood‑pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM‑, CMEADM2‑, CMEADM+ (surface charges:‑10.4, ‑41.0 and +9.6mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ‑11.5mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel=(SI post‑contrast‑SI pre‑contrast/SI pre‑contrast)x100. Following injection with the CMEADMs, but not with USPIO, the invivo pooling time was prolonged to >300min. No significant differences were attributable to the electric charge among the CMEADM‑, CMEADM2‑ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently‑charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

Negatively charged superparamagnetic iron oxide nanoparticles: a new blood-pooling magnetic resonance contrast agent

Our purpose was to investigate the utility of superparamagnetic iron-oxide nanoparticles (SPIO) as a blood-pooling contrast agent at magnetic resonance imaging (MRI). We studied four contrast agents: carboxymethyl-diethylaminoethyl dextran magnetite SPIO (CMEADM-S, diameter 54 nm), negatively charged CMEADM ultrasmall SPIO (CMEADM-U, 32 nm), alkali-treated dextran magnetite SPIO (ATDM-S, 55 nm), and ATDM ultrasmall SPIO (ATDM-U, 28 nm) carrying a neutral charge. Each contrast agent (80 μmol/kg) was injected intraperitoneally into apolipoprotein E (apoE) mice and the tissue iron concentration was measured 30-, 60-, 180-, and 300-min later by nuclear MR. For MR angiographic (MRA) evaluation, we injected the agents into the auricular vein of four groups of 15 rabbits. Immediately and 30-, 60-, 180-, and 300-min later, three rabbits from each group were subjected to MRI. The organ/background signal ratio (SR) was calculated. Statistical analyses were performed with Tukey's honestly significant difference (HSD) test. At 60 and 180 min, blood-iron concentration of CMEADM-U was significantly different from other contrast agents. In the abdominal aorta and inferior vena cava, SR of CMEADM-U was higher at 180 and 300 min than of the other contrast agents. In the thoracic aorta, there was no difference in SR at 300 min between CMEADM-U and CMEADM-S. Negatively charged SPIO nanoparticles may be useful as a blood-pooling contrast agent.

Impact of surface coating and particle size on the uptake of small and ultrasmall superparamagnetic iron oxide nanoparticles by macrophages

PurposeMagnetic resonance imaging (MRI) using contrast agents like superparamagnetic iron oxide (SPIO) is an extremely versatile technique to diagnose diseases and to monitor treatment. This study tested the relative importance of particle size and surface coating for the optimization of MRI contrast and labeling efficiency of macrophages migrating to remote inflammation sites.Materials and methodsWe tested four SPIO and ultrasmall superparamagnetic iron oxide (USPIO), alkali-treated dextran magnetite (ATDM) with particle sizes of 28 and 74 nm, and carboxymethyl dextran magnetite (CMDM) with particle sizes of 28 and 72 nm. Mouse macrophage RAW264 cells were incubated with SPIOs and USPIOs, and the labeling efficiency of the cells was determined by the percentage of Berlin blue-stained cells and by measuring T2 relaxation times with 11.7-T MRI. We used trypan blue staining to measure cell viability.ResultsAnalysis of the properties of the nanoparticles revealed that ATDM-coated 74 nm particles have a lower T2 relaxation time than the others, translating into a higher ability of MRI negative contrast agent. Among the other three candidates, CMDM-coated particles showed the highest T2 relaxation time once internalized by macrophages. Regarding labeling efficiency, ATDM coating resulted in a cellular uptake higher than CMDM coating, independent of nanoparticle size. None of these particle formulations affected macrophage viability.ConclusionThis study suggests that coating is more critical than size to optimize the SPIO labeling of macrophages. Among the formulations tested in this study, the best MRI contrast and labeling efficiency are expected with ATDM-coated 74 nm nanoparticles.

Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential

We developed a dextran-magnetite conjugated cisplatin (DM-Cis) complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron). The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH) device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip) and placed magnets subcutaneously (sc). In group 2 we injected saline (ip) and placed magnets (sc). In group 3 we injected DM-Cis (ip) and placed a sc incision (sham). The control (group 4) received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (μm(2)) were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 μg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05) in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a magnetically-accumulated anticancer drug with hyperthermic effects.

Estimation of Density of Low-Concentration Magnetic Fluid by a Needle-Type GMR Sensor for Medical Applications

The size, shape and composition of magnetic nanoparticles make it an attractive tool in medical applications. Low concentration Dextran Magnetite (DM)® or magnetic fluid is widely used for biomedical applications. This paper reports experimental apparatus designed for testing low concentration magnetic fluid, results obtained by experimentation utilizing a simple, novel and low invasive needle-type spin-valve giant magnetoresistance (SV-GMR) sensor and numerical analysis for comparison with the experimental results obtained. Low concentration magnetic fluid weight density is estimated by the difference between the magnetic flux density inside and outside a magnetic fluid filled cavity. The results show that the proposed technique employing the needle sensor has a good potential to be used in biomedical applications such as hyperthermia therapy in cancer treatment and targeted drug delivery, for low concentration magnetic fluid weight density measurements in-vivo.

Pulp ablation therapy by inductive heating: heat generation characteristics in the pulp cavity

This study was performed to clarify the usefulness of inductive heating system for the new endodontic therapy. Dextran magnetite complex (DM) suspensions were injected into the root canal of a permanent tooth, and the tooth was heated up to about 55.0 degrees C by alternating-current magnetic field. The time until the temperature in the pulp cavity reached 55.0 degrees C was 328 +/- 26 s (mean +/- s.d., n = 8) in the 56 mg as Fe ml(-1) of DM concentration. The temperature in the pulp cavity could be maintained at 53.5-59.0 degrees C for 1200 s by changing the magnetic field intensity safely, while temperature elevations of the dental surface on the coronal and apical sides were 4.9 degrees and 3.7 degrees C, respectively. Thus, this inductive heating system, which has the possibility of selective heating, might be useful for eliminating residues of pulp as a new ablation therapy.

Preparation of magnetite–dextran microspheres by ultrasonication

An improved method of preparing magnetite–dextran microspheres by ultrasonication is proposed. Several parameters were evaluated and the characteristics of the microspheres investigated by scanning electron microscope (SEM), atomic force microscope (AFM), particle size analyzer and magnetometer. The results show that the initial Fe/dextran ratio is the most effective parameter for both the size and the magnetic properties.

Antitumor effect of new local hyperthermia using dextran magnetite complex in hamster tongue carcinoma.

This study was performed to clarify the usefulness of Dextran magnetite (DM) for the oral cancer hyperthermia. Tumors were induced in golden hamster tongue by 9,10-dimethyl 1-1,2-benzanthracene (DMBA) application. DM suspension was locally injected into the tumor-bearing tongue and tongues were heated up to 43.0-45.0 degrees C, by AC magnetic field of 500 kHz. The average time taken for the temperature to rise to 43.0 degrees C or above was 162 s (n = 17) at the margin of the tumor and 420 s (n = 17) at the center of the tumor. According to the tumor volume, the time required for an increase in the central temperature of tumor to 43.0 degrees C tended to be prolonged. Both temperatures could be maintained at approximately 43.0-45.0 degrees C for 30 min. The inhibition of the growth of tongue carcinoma in the four-time heating group was significantly greater than in the control group (P < 0.01). Moreover, the survival rate was significantly higher in the heated groups than in the control group (P < 0.01). Histological examination revealed a brown uniform DM accumulation at the stroma in the margin of the tumors. Many of tumor cells disappeared at the site adjacent to this accumulation. These results strongly suggest the usefulness of this local hyperthermic system in the oral region that is accessible to this treatment.

デキストラン・マグネタイト複合体 (DM) を用いた携帯型誘導加温装置の開発

デキストラン・マグネタイト複合体 (DM) を用いた携帯型誘導加温装置の開発

In utero time-course assessment of mouse embryo development using high resolution magnetic resonance imaging.

Magnetic resonance microscopy, a non-invasive imaging technique was used for a longitudinal follow-up of mouse embryonic development in utero and for the assessment of embryonic kidney function using 50 nm magnetite dextran particles. Even though the morphologic proton images obtained were still far from classical histological slices quality, an in-plan resolution of 195 microm was achieved for a slice thickness of 800 microm. Mouse embryos sub-structures such as the fourth ventricle, the mesencephalic vesicle, the aorta or the liver can be revealed as early as E11/12. Heart, diaphragm, spinal cord, third, fourth and lateral ventricles were unambiguously seen at E13/14; whereas skeleton, tail, kidney and digit can only be seen from E15/16. Kidney and bladder were certainly identified from E16 on. MR microscopy offers a possibility for in utero phenotyping of mice and can therefore be a powerful tool for post-genomic applications.

Dextran-magnetite complex: temperature dependence of its NMR relaxivity.

The NMR relaxivity of proton by dextran-magnetite (DM) complex was examined at temperatures from 20 to 80 degrees C. The decrease in T1 relaxivity with increasing temperature is due to the thermal activation of motion of water molecules in and/or surrounding DM particle. The decrease in magnetization of magnetite core is the secondary effect. The temperature dependence of T1 relaxivity was found to depend on molecular weight of dextran. The motion of dextran chains binding to core may affect the thermal activation of "heavy water" interacted with dextran. The Arrhenius plots of T1 relaxivity showed different slopes at 20-40 degrees C and 50-80 degrees C, while, no change in slope was observed for Fe(NO3)3, CuSO4 and Gd-DTPA solutions.

Does the endolymph pass through the base of the cupula?

Whether the endolymph of the semicircular canal passes the cupular partition or not was examined using the lateral semicircular canal system of adult pigeons (Columba livia). By applying various pressures by means of injection of a dye solution through the membranous canal, it was found that the dye solution was seen to pass the cupula even under very low pressures when the pressure was increased gradually. When pulled by a magnet, the ultrafine particles of the dextran magnetite contained in the injected fluid were found to pass through the subcupular space without evident increase of the ampullary pressure.

Enhancing fMRI contrast in awake-behaving primates using intravascular magnetite dextran nanopartieles.

Functional MRI in awake-behaving primates is an emerging tool for bridging the gap between human fMRI and neurophysiology information from nonhuman primates. We report the use of magnetite dextran nanoparticles (Feridex) as a blood-pool agent to enhance fMRI contrast-to-noise (CNR) in primate FMRI. The intravascular half-life of the magnetite dextran was long compared to lanthanide chelates (T(1/2) = 198 min) with shortened T(2) relaxation observed in blood and cerebral cortex. Greater than 3-fold enhancement in the percentage MR signal change was observed using nanoparticles (13%) compared with conventional BOLD fMRI (4%). The calculated regional cerebral blood volume in macaque primary visual cortex increased 32% with photic stimulation. The increased CNR allows greater flexibility in the design of awake-behaving primate fMRI studies with the potential for improvements in resolution and significantly shortened imaging times.

New local hyperthermia using dextran magnetite complex (DM) for oral cavity: experimental study in normal hamster tongue

The possibility of dextran magnetite complex (DM) as a new hyperthermic material was examined in this study. DM suspension of 56 mg ml(-1) iron concentration was locally injected into the normal tongue of golden hamster. DM injected tongues were heated by 500 kHz alternating current (AC) magnetic field and its serial changes in temperature were recorded at 30-s intervals. The temperature of DM injected tongue was maintained at about 43.0-45.0 degrees C for 30 min by changing the AC magnetic field intensity. While temperature elevations of the contralateral tongue and the rectum were only of minor degree. In experiment on the extent of heating area, there was correlation between volume of black stain area and amount of the injected DM suspension (Y = - 18.1 + 1.94X, r = 0.931, P < 0.0001, n = 9 ). Histological examination after heating revealed brown uniform DM accumulation in the connective tissue between fibers of the tongue muscle. Except for vascular dilatations, no tissue damage was seen in the heated tongue. Thus, DM which has the possibility of selective and uniform heating in local hyperthermia might be useful for oral cancer therapy.

New local hyperthermia using dextran magnetite complex (DM) for oral cavity: experimental study in normal hamster tongue

The possibility of dextran magnetite complex (DM) as a new hyperthermic material was examined in this study. DM suspension of 56 mg ml −1 iron concentration was locally injected into the normal tongue of golden hamster. DM injected tongues were heated by 500 kHz alternating current (AC) magnetic field and its serial changes in temperature were recorded at 30-s intervals. The temperature of DM injected tongue was maintained at about 43.0–45.0°C for 30 min by changing the AC magnetic field intensity. While temperature elevations of the contralateral tongue and the rectum were only of minor degree. In experiment on the extent of heating area, there was correlation between volume of black stain area and amount of the injected DM suspension (Y =−18.1 + 1.94X, r= 0.931, P < 0.0001, n= 9). Histological examination after heating revealed brown uniform DM accumulation in the connective tissue between fibers of the tongue muscle. Except for vascular dilatations, no tissue damage was seen in the heated tongue. Thus, DM which has the possibility of selective and uniform heating in local hyperthermia might be useful for oral cancer therapy.

Passage of dextran magnetite nanoparticles through the subcupular space of the pigeon.

We examined the permeability of the subcupular space for endolymph flow in the pigeon. A new technique was developed in which nanoparticles consisting of dextran magnetite were attracted by use of a magnet, instead of injecting a dye solution. The method was revealed to prevent an excess pressure application by the injection of dye solution. The Berlin blue color resulting from the dextran magnetite nanoparticles was found mainly within the subcupular space contacting with the sensory hairs. Further formation of the Berlin blue was found within the sensory cells. The result supports the idea that the fluid passes through the subcupular space.

Dextran-magnetite complex: conformation of dextran chains and stability of solution.

Three kinds of dextran-magnetite (DM) complexes were prepared using alkali-treated dextrans with molecular weights of 1900, 4200 and 9600, respectively. The number of dextrans binding to a magnetite core was determined. The number was proportional to the area of core surface and the area occupied by a dextran was 2.5 nm2 for molecular weight of 1900, 2.8 for 4200 and 3.8 for 9600. The binding of dextrans to core may be conditioned by the conformation of dextran chains in water (possibly by the steric hindrance between dextrans covering core). Stability of the DM solution was examined at 80 degrees C. Aggregation and/or precipitation of DM particles were observed within two weeks. The stability of DM solution was found to increase with increasing molecular weight of dextran. The dissociation of dextran from the core may cause the aggregation and subsequent precipitation of DM particles (the dissociation constant at 20 degrees C, 3.7 x 10(-6) for a molecular weight of 1900 and 5.4 x 10(-7) for 9600).