Pulsed magneto-motive ultrasound imaging to detect intracellular trafficking of magnetic nanoparticles

As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular accumulation of nanoparticles-an important part of cell-nanoparticle interaction-has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique-pulsed magneto-motive ultrasound (pMMUS)-to identify intracellular accumulation of endocytosed magnetic nanoparticles. In pMMUS imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to the signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e.?intracellular accumulation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular accumulation non-invasively and in real-time.     

Biocompatible nanoclusters of <Emphasis Type="Italic">O</Emphasis>-carboxymethyl chitosan-coated Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles: synthesis,characterization and magnetic heating efficiency

In this work, we developed a polymer encapsulation of Fe₃O₄ nanoparticles as a core–shell nanocluster with different sizes to investigate the cluster structure effect on their magnetic properties and magnetic heating behavior. Well-dispersed nanoclusters of O-carboxymethyl chitosan-coated Fe₃O₄ nanoparticles were synthesized by microwave-assisted co-precipitation. The cluster sizes were tunable by varying the concentration of polymers used during synthesis. Nanoclusters present superparamagnetic behavior at room temperature with a reduction in saturation magnetization as a consequence of coating layer. The shift of blocking temperature to the higher value with increasing clusters size shows the stronger magnetic interaction in larger magnetic clusters. In a low alternating magnetic field with frequency of 178 Hz and amplitude of 103 Oe, nanoclusters offer a high heating efficiency. A maximum specific absorption rate of 204 W/g is observed in the sample with hydrodynamic size of 53 nm. In vitro cytotoxicity analysis performed on HeLa cells verified that nanoclusters show a good biocompatibility and can be an excellent candidate for applications in hyperthermia cancer treatment.     

Synthesis of core-shell nanoclusters with high magnetic moment for biomedical applications

Biocompatible magnetic nanoparticles have been found to be promising in several biomedical applications for tagging, imaging, sensing, and separation in recent years. Most magnetic particles or beads currently used in biomedical applications are based on ferromagnetic iron oxides with very low specific magnetic moments of about 20-30 emu/g. Here, we report a new approach to synthesize monodispersive core-shell nanostructured clusters with high specific magnetic moments above 200 emu/g. The Fe nanoclusters, ranging in size from 2 to 100 nm, are produced from a newly developed cluster source and go to a deposition chamber, where a chemical reaction starts, and the nanoclusters are coated with Fe oxides. High-resolution transmission electron microscopy images show the coatings are very uniform. The core-shell nanoclusters are superparamagnetic at room temperature for sizes less than 12 nm, and have the coercivity of about 1.5 kOe at low temperature (5 K).     

Detection of magnetic nanoparticles in tissue using magneto-motive ultrasound

The purpose of this study was to demonstrate the magneto-motive ultrasonic detection of superparamagnetic iron oxide (SPIO) nanoparticles as a marker of macrophage recruitment in tissue. The capability of ultrasound to detect SPIO nanoparticles (core diameter ～20?nm) taken up by murine liver macrophages was investigated. Eight mice were sacrificed two days after the intravenous administration of four SPIO doses (1.5, 1.0, 0.5, and 0.1?mmol Fe/kg body weight). In the iron-laden livers, ultrasound Doppler measurements showed a frequency shift in response to an applied time-varying magnetic field. M-mode scan and colour power Doppler images of the iron-laden livers also demonstrated nanoparticle movement under focused magnetic field excitation. In the livers of two saline injected control mice, no movement was observed using any ultrasound imaging modes. The results of our experiments indicate that ultrasound imaging of magneto-motive excitation is a candidate imaging modality to identify tissue-based macrophages containing SPIO nanoparticles.     

肿瘤靶向纳米四氧化三铁造影剂的制备及其磁共振成像应用

环氧氯丙烷交联法制备交联葡聚糖与多肽偶联的肿瘤新生血管靶向的纳米Fe3O4造影剂,考察其体内肿瘤靶向性并进行磁共振成像试验。以共沉淀法制备6～8nm的Fe3O4粒子,采用油酸钠和葡聚糖二次包覆,用环氧氯丙烷使葡聚糖交联并与靶向多肽偶联,进行了肿瘤细胞结合实验和荷瘤动物磁共振成像实验。结果表明,包覆后纳米Fe3O4复合粒子为20～30nm,水动力学粒径小于80nm,仍表现为超顺磁性;葡聚糖交联的时间4～8h,造影剂在体内血浆半衰期从2.8h延长到6.2h;主要通过肝脏和肾脏代谢。与无靶的比较,靶向多肽偶联后与肿瘤细胞特异性结合能力提高了10～30倍,MR成像信号密度是无靶的3.68倍。     

Superparamagnetic γ-Fe2O3 nanoclusters in silicate matrices

Superparamagnetic γ-Fe₂O₃ nanoclusters have been synthesized on the surfaces of activated layered silica (ALS) and activated mesoporous silica gel (AMS). According to 300-K Mössbauer spectroscopy data and magnetization measurements between 2 and 300 K, the size of the γ-Fe₂O₃ nanoclusters increases from 2–3 to s~6–8 nm as the Fe content of ALS increases from 2.5 and 4.5 to 18.5 wt %. The 2.5 wt % Fe/ALS sample contains superparamagnetic γ-Fe₂O₃ nanoclusters uniform in size and magnetic properties. The nanoclusters produced on the AMS surface are larger and are nonuniform in magnetic properties.     

Fluorescent magnetic hybrid nanoprobe for multimodal bioimaging

A fluorescent magnetic hybrid imaging nanoprobe (HINP) was fabricated by the conjugation of superparamagnetic Fe3O4 nanoparticles and visible light emitting (～600 nm) fluorescent CdTe/CdS quantum dots (QDs). The assembly strategy used the covalent linking of the oxidized dextran shell of magnetic particles to the glutathione ligands of QDs. The synthesized HINP formed stable water-soluble colloidal dispersions. The structure and properties of the particles were characterized by transmission electron and atomic force microscopy, energy dispersive x-ray analysis and inductively coupled plasma optical emission spectroscopy, dynamic light scattering analysis, optical absorption and photoluminescence spectroscopy, and fluorescent imaging. The luminescence imaging region of the nanoprobe was extended to the near-infrared (NIR) (～800 nm) by conjugation of the superparamagnetic nanoparticles with synthesized CdHgTe/CdS QDs. Cadmium, mercury based QDs in HINP can be easily replaced by novel water-soluble glutathione stabilized AgInS2/ZnS QDs to present a new class of cadmium-free multimodal imaging agents. The observed NIR photoluminescence of fluorescent magnetic nanocomposites supports their use for bioimaging. The developed HINP provides dual-imaging channels for simultaneous optical and magnetic resonance imaging.     

The hydrothermal synthesis of super-paramagnetic barium hexaferrite particles

Superparamagnetic Ba-hexaferrite nanoparticles were prepared using modified hydrothermal synthesis. The precursor and hydroxide [OH⁻] concentrations were optimized and the synthesis temperature and time were drastically reduced. The size and the morphology of synthesized nanoparticles was confirmed by transmission electron microscopy (TEM) images. The crystal structure of the nanoparticles was characterized by X-ray diffraction data. Powders synthesized at 160 °C exhibit a bimodal particle size distribution while those synthesized at T_S = 150 °C show a monomodal particle size distribution. Zero-field-cooling (ZFC) and field-cooling (FC) magnetization measurements were performed using a superconducting quantum interference device magnetometer from 2 to 300 K to investigate the magnetic properties of nanoparticles. The FC/ZFC magnetization measurements showed a typical superparamagnetic behavior. The synthesized superparamagnetic particles exhibit a disc-like shape, in average 11 nm wide and 3 nm thick with a room temperature magnetization of approximately 10 Am²/kg at 5 T.     

Effect of Synthesis Parameters on the Properties of Superparamagnetic Iron Oxide Nanoparticles

Iron oxide nanoparticles were coprecipitated in air medium using different sodium hydroxide (NaOH) concentrations, and their structural and magnetic properties were studied. It was observed that the precipitation of superparamagnetic iron oxide nanoparticles could be achieved above a critical NaOH concentration. This was followed by the investigation of the effect of the stirring rate on the structural and magnetic properties of the nanoparticles precipitated at 8.5?M NaOH and over. Morphological observation made by a transmission electron microscope (TEM) showed that the particle size of iron oxide nanoparticles was around 7.5?nm. Magnetization curves measured by a vibrating sample magnetometer showed zero coercivity indicating that the samples are superparamagnetic and the highest saturation magnetization (70.4?emu/g) was obtained at the stirring rate of 1100?rpm. The mean particle sizes of iron oxide nanoparticles calculated from the magnetization data are found to be consistent with the particle sizes obtained from the TEM images.     

不同粒径超顺磁性氧化铁纳米粒子的合成及其在交变磁场中的磁热效应

采用多醇热解法制备3种不同粒径的超顺磁性氧化铁纳米粒子(SPIONs),合成的SPIONs含Fe_3O_4晶相,分散性好,平均粒径分别为8.7,12.6nm和15.3nm,且在300K下,3种SPIONs均呈超顺磁性。将不同粒径、不同浓度的SPIONs水分散液置于频率为425kHz、磁场强度为5.3kA·m^-1的交变磁场(ACMF)中进行升温实验。探讨比能量吸收率值与SPIONs粒径之间的关系,计算布朗弛豫时间及尼尔弛豫时间。结果表明:SPIONs水分散液的升温速率随SPIONs的粒径增大而增大,初始温度为20℃时,粒径为8.7,12.6nm和15.3nm的SPIONs水分散液(2mg·mL^-1)在480s内温度分别升高了25,27,35℃。尼尔弛豫时间比布朗弛豫时间小,说明磁热效应主要来自于尼尔弛豫损耗。SPIONs粒径越大,比能量吸收率SAR值越高,最高可达810W·g^-1,且SAR值与SPIONs水分散液的浓度呈负相关关系。     

Preparation and characterization of Ni-nitrilotriacetic acid bearing poly(methacrylic acid) coated superparamagnetic magnetite nanoparticles

Stable superparamagnetic magnetite (Fe3O4) nanoparticles were synthesized via co-precipitation in the presence of poly(methacrylic acid) (PMAA) in aqueous solution. The polymer coated Fe3O4 nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis, and vibrating sample magnetometry (VSM) techniques. These measurements reveal the presence of magnetite nanoparticles with a size of approximately 8 nm inside the PMAA matrix. The magnetization value of these superparamagnetic nanoparticles at room temperarure and 7 T was measured as about 40 emu/g. PMAA-coated Fe3O4 nanoparticles were further assembled with Ni-chelate through a reaction between a primary amine-bearing NTA (nitrilotriacetic acid) ligand and carboxy-functional groups of PMAA. NTA-PMAA-coated magnetite nanoparticles were then loaded with nickel ions and characterized using FTIR. The average amount of binded Ni on the surface of the NTA-modified PMAA coated Fe3O4 was calculated as 1.65 +/- 0.3 x 10(-6) mol nickel(II) ions per g of the magnetic particles from the inductively coupled plasma optical emission spectroscopy (ICP-OES) measurements.     

Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging (MRI) contrast agents or in drug delivery applications. In this study, a novel approach to prepare magnetic polymeric nanoparticles with magnetic core and polymeric shell using inverse microemulsion polymerization process is reported. Poly(ethyleneglycol) (PEG)-modified superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared inside the aqueous cores of AOT/n-Hexane reverse micelles and characterized by various physicochemical means such as transmission electron microscopy (TEM), infrared spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM), and ultraviolet/visible spectroscopy. The inverse microemulsion polymerization of a polymerizable derivative of PEG and a cross-linking agent resulted in a stable hydrophilic polymeric shell of the nanoparticles. The results taken together from TEM and AFM studies showed that the particles are spherical in shape with core-shell structure. The average size of the PEG-modified nanoparticles was found to be around 40-50 nm with narrow size distribution. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles with saturation magnetization values between 45-50 electromagnetic units per gram. The cytotoxicity profile of the nanoparticles on human dermal fibroblasts as measured by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the particles are nontoxic and may be useful for various in vivo and in vitro biomedical applications.     

Solvothermal synthesis and characterization of size-controlled monodisperse Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles

Monodisperse Fe₃O₄ nanoparticles with narrow size distribution could be successfully synthesized in large quantities by a facile solvothermal synthetic method in the presence of oleic acid and oleylamine. Well-defined assembly of uniform nanoparticles with average sizes of 8 nm can be obtained without a further size-selection process. The sizes of final products could be readily tuned from 5 to 12 nm by adjusting the experimental parameters such as reaction time, temperature, and surfactants. The phase structures, morphologies, and magnetic properties of the as-prepared products were investigated in detail by X-ray diffraction, transmission electron microscopy, selected area electron diffraction, high-resolution transmission electron microscopy, and magnetometry with a superconducting quantum interference device. The magnetic study reveals that the as-synthesized nanoparticles are ferromagnetic at 2 K while they are superparamagnetic at 300 K.     

Size-dependent nonlinear weak-field magnetic behavior of maghemite nanoparticles

The magnetic behavior at room temperature of maghemite nanoparticles of variable sizes (from 7 to 20 nm) is compared using a conventional super quantum interference device (SQUID) and a recently patented technology, called MIAplex. The SQUID usually measures the magnetic response versus an applied magnetic field in a quasi-static mode until high field values (from -4000 to 4000 kA m(-1)) to determine the field-dependence and saturation magnetization of the sample. The MIAplex is a handheld portable device that measures a signal corresponding to the second derivative of the magnetization around zero field (between -15 and 15 kA m(-1)). In this paper, the magnetic response of the size series is correlated, both in diluted and powder form, between the SQUID and MIAplex. The SQUID curves are measured at room temperature in two magnetic field ranges from -4000 to 4000 kA m(-1) (-5T to 5T) and from -15 to 15 kA m(-1). Nonlinear behavior at weak fields is highlighted and the magnetic curves for diluted solutions evolve from quasi-paramagnetic to superparamagnetic behavior when the size of the nanoparticles increases. For the 7-nm sample, the fit of the magnetization with the Langevin model weighted with log-normal distribution corresponds closely to the magnetic size. This confirms the accuracy of the model of non-interacting superparamagnetic particles with a magnetically frustrated surface layer of about 0.5 nm thickness. For the other samples (10-nm to 21-nm), the experimental weak-field magnetization curves are modeled by more than one population of magnetically responding species. This behavior is consistent with a chemically uniform but magnetically distinct structure composed of a core and a magnetically active nanoparticle canted shell. Accordingly the weak-field signature corresponds to the total assembly of the nanoparticles. The impact of size polydispersity is also discussed.     

Magnetic hollow mesoporous silica nanospheres: facile fabrication and ultrafast immobilization of enzymes

Hollow mesoporous silica nanospheres with large pore size of around 11 nm have been synthesized by a structural difference based selective etching strategy, and the highly dispersed hydrophobic Fe3O4 nanoparticles with a particle size of 5 nm were then impregnated into hollow cores of nanospheres through these large pores by a vacuum impregnation technique. The structural characteristics of obtained magnetic composites were characterized by X-ray diffraction (XRD), Fourier Transform Infrared (FTIR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Selected Area Electron Diffraction (SAED), Ultraviolet-visible (UV-Vis) and Vibrating Sample Magnetometer (VSM). The results show that the obtained Fe3O4-hollow mesoporous silica composites exhibit superparamagnetic property with saturation magnetization value of 4.17 emu/g. Furthermore, the obtained supports show ultrafast immobilization of hemoglobin and the immobilized enzymes are not denatured, indicating that the superparamagnetic hollow mesoporous silica spheres are excellent support for immobilization of enzymes with magnetic recycling property.     

Synthesizing cysteine-coated magnetite nanoparticles as MRI contrast agent: Effect of pH and cysteine addition on particles size distribution

Cysteine capped magnetite nanoparticles (10 to 20 nm) were synthesized via coprecipitation method under ultrasonic irradiation. The influence of pH value of the solution and cysteine addition on the size distribution and hydrodynamic size of nanoparticles were studied via TEM and PCS methods, respectively. The crystal structure and magnetic properties of the nanoparticles were characterized by XRD and VSM techniques, respectively. Coating density was calculated using TGA and TEM results. Cytotoxicity assessment performed by incubation of L929 cells, confirmed that ferrofluids are biocompatible. MRI studies conducted on rats demonstrated suitability of synthesized nanoparticles as contrast agents, especially for imaging of the lymph nodes.     

Electron transfer behavior of monolayer protected nanoclusters and nanowires of silver and gold

Understanding the electron transfer behavior of nanometer sized, both metallic and semiconducting particles and wires is important due to the fundamental interest in size and shape dependent electronic properties and also because of its applications in nano-electronic devices like single electron transistors and molecular switches. Monolayer protected nanoclusters enable one simple and elegant method of synthesis of these types of metallic and semiconducting materials using interfacial chemistry as has been successfully used in several applications ranging from catalysis to molecular electronics. The success of this type of nanostructured materials is due in part to the well known protecting/stabilizing action of the ligands (also known as surface passivating/capping agents), which facilitate the synthesis and processing of these hydrophobic colloids in solution form. The present article discusses the electron transfer behavior of silver nanowires and nanoparticles with varied sizes. In particular, we have investigated the electrochemical properties of silver nanowires (diameter 70 nm, length several micrometers) and compared with the behavior of similar relatively larger sized nanoparticles (size 40 nm). A critical analysis of the redox behavior of silver nanowires and nanoparticles is presented in aqueous medium under various electrolytic conditions along with a comparison of analogous properties of smaller sized (2-7 nm) silver and gold nanoclusters.     

Investigation of magnetically enhanced swelling behaviour of superparamagnetic starch nanoparticles

The present study follows a novel strategy for the preparation of superparamagnetic nanoparticles of cross-linked starch impregnated homogeneously with nanosized iron oxide. The prepared magnetic nanoparticles were characterized by infra-red (FTIR) spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction and magnetization studies. The size of the magnetic polymeric particles was found to lie in the range of 20–80 nm, and they exhibited superparamagnetic properties. The particles were allowed to swell in phosphate buffer saline (PBS) and the influence of factors such as chemical composition of nanoparticles, pH and temperature of the swelling bath and applied magnetic field was investigated on the water intake capacity of the nanoparticles. The prepared nanoparticles showed potential to provide a possible option for controlled and targeted delivery of anticancer drugs, applying external magnetic field.     

Manipulation and tracking of superparamagnetic nanoparticles using MRI

The use of magnetic fields in magnetic resonance imaging (MRI) for the tracking and delivery of chemotherapeutics bound to superparamagnetic nanoparticles offers a promising method for the non-invasive treatment of inoperable tumours. Here we demonstrate that superparamagnetic magnetite nanoparticles fabricated by an easily scalable method can be driven and tracked in real time at high velocities in vitro using MRI hardware. Force balance calculations are consistent with the magnetic properties of individual 10 nm diameter particles that move collectively as micron sized agglomerates with hydrodynamic diameter similar to that inferred from zero-magnetic-field dynamic light scattering measurements.     

Magnetic force microscopy of superparamagnetic nanoparticles

The use of magnetic force microscopy (MFM) to detect probe-sample interactions from superparamagnetic nanoparticles in vitro in ambient atmospheric conditions is reported here. By using both magnetic and nonmagnetic probes in dynamic lift-mode imaging and by controlling the direction and magnitude of the external magnetic field applied to the samples, it is possible to detect and identify the presence of superparamagnetic nanoparticles. The experimental results shown here are in agreement with the estimated sensitivity of the MFM technique. The potential and challenges for localizing nanoscale magnetic domains in biological samples is discussed.