In vitro study of magnetic nanoparticles as the implant for implant assisted magnetic drug targeting

Magnetic nanoparticle (MNP) seeds were studied in vitro for use as an implant in implant assisted-magnetic drug targeting (IA-MDT). The magnetite seeds were captured in a porous polymer, mimicking capillary tissue, with an external magnetic field (70 mT) and then used subsequently to capture magnetic drug carrier particles (MDCPs) (0.87 μm diameter) with the same magnetic field. The effects of the MNP seed diameter (10, 50 and 100 nm), MNP seed concentration (0.25-2.0 mg/mL), and fluid velocity (0.03-0.15 cm/s) on the capture efficiency (CE) of both the MNP seeds and the MDCPs were studied. The CE of the 10 nm MNP seeds was never more than 30%, while those of the 50 and 100 nm MNP seeds was always greater than 80% and in many cases exceeded 90%. Only the MNP seed concentration affected its CE. The 10 nm MNP seeds did not increase the MDCP CE over that obtained in the absence of the MNP seeds, while the 50 and 100 nm MNP seeds increased significantly, typically by more than a factor of two. The 50 and 100 nm MNP seeds also exhibited similar abilities to capture the MDCPs, with the MDCP CE always increasing with decreasing fluid velocity and generally increasing with increasing MNP seed concentration. The MNP seed size, magnetic properties, and capacity to self-agglomerate and form clusters were key properties that make them a viable implant in IA-MDT.     

Synthesis of amino-group functionalized superparamagnetic iron oxide nanoparticles and applications as biomedical labeling probes

Superparamagnetic iron oxide (SPIO) nanoparticles were synthesized by coprecipitation technique and further functionalized with amino-group to obtain amino-group functionalized (amino-SPIO) nanoparticles. The X-ray diffraction results reveal the structure of amino-SPIO nanoparticles, from which the average iron core diameter is approximately 10 nm by calculation; while Zetasizer reveals their hydrodynamic diameter are mainly distributed in the range of 40?C60 nm. These nanoparticles can be taken up by liver tissue, resulting in dramatically darkening of liver tissue under T2-magnetic resonance imaging (MRI). The spin?Cspin relaxivity coefficient of these nanoparticles is 179.20 mM^?1 s^?1 in a 1.5 T magnetic resonance system. In addition, amino-SPIO nanoparticles were conjugated to Tat (FITC) peptide and incubated with neural stem cells in vitro, the authors can detect the positive-labeling (labeled) neural stem cells showing green fluorescence, which indicates Tat (FITC) peptide-derivated amino-SPIO nanoparticles are able to enter cells. Furthermore, it was also find significant negative T2 contrast enhancement when compared with the non-nanoparticles-labeled neural stem cells in T2-weighted MRI. The amino-SPIO nanoparticles show promising potential as a new type of labeling probes, which can be used in magnetic resonance-enhanced imaging and fluorescence diagnosis.     

Frequency-domain birefringence measurement of biological binding to magnetic nanoparticles

Optical detection of the frequency-dependent magnetic relaxation signal is used to monitor the binding of biological molecules to magnetic nanoparticles in a ferrofluid. Biological binding reactions cause changes in the magnetic relaxation signal due to an increase in the average hydrodynamic diameter of the nanoparticles. To allow the relaxation signal to be detected in dilute ferrofluids, measurements are made using a balanced photodetector, resulting in a 25 μV/√Hz noise floor, within 50% of the theoretical limit imposed by photon shot noise. Measurements of a ferrofluid composed of magnetite nanoparticles coated with anti-IgG antibodies show that the average hydrodynamic diameter increases from 115.2 to 125.4 nm after reaction with IgG.     

A novel magnetic fluid based on starch-coated magnetite nanoparticles functionalized with homing peptide

Preparation and characterization in vitro and in vivo of a novel magnetic fluid based on starch-coated magnetite nanoparticles functionalized with homing peptide is reported in this paper. Precursory magnetic fluids stabilized with starch were prepared, in a polymeric starch matrix, by controlled chemical coprecipitation of magnetite phase from aqueous solutions. The average hydrodynamic diameter of starch-coated iron oxide nanoparticles (SIONs) was 46 nm. As a homing peptide, A54 is the most effective peptide specific to the human hepatocellular carcinoma cell line BEL-7402. Final magnetic fluids were obtained through chemical coupling of homing peptide labeled with 5-carboxyl-fluorescein (FAM-A54) and SIONs. Magnetic measurements showed the saturation magnetization value of SIONs amounted to 45 emu/g and the FAM-A54-coupled SIONs showed a good magnetic response in magnetic field. The results of experiments in vitro and in vivo showed that SIONs were endowed with specific affinity to corresponding tumor cells after coupling with FAM-A54 and the FAM-A54-coupled SIONs could be accumulated in the tumor tissue with more efficiency than individual magnetic targeting or biomolecular targeting. This novel magnetic fluid with dual function has great potential applications in diagnostics and therapeutics of human tumor such as drug targeting, magnetic hyperthermia, and magnetic resonance imaging.     

Synthesis of Aucore–Agshell type bimetallic nanoparticles for single molecule detection in solution by SERS method

This paper reports the evolution of a new class of core–shell type, that is, Au_core–Ag_shell bimetallic nanoparticles by seed mediated technique for surface enhanced Raman scattering (SERS) study. Here it is demonstrated how to control the thickness of Ag-shell with the variation of gold seed (15 nm) to Ag ion concentration which in turn control the particle size in the range from 50 to 100 nm with increase of shell thickness. For 50 nm core–shell particles the thickness of the shell was 17 nm, for 70 nm particles the thickness was 27 nm and for 100 nm the thickness was 42 nm. SERS study was performed on those particles using the analyte crystal violet (CV) to examine the impact of the size and field effects of the bimetallics on SERS spectra. A surprising finding is that a small particle as low as 50 nm have been found to be highly efficient for SERS, even it enables the detection of a selected dye molecule down to single molecular level. The sensitivity of the SERS detection limit has been improved further with an activating reagent like NaCl. The newly modeled bimetallic system establishes a relationship between the local electromagnetic (EM) field effect and chemical effect (CE) on the enhancement of SERS spectra, which provides further insight into the enhancement mechanism of SERS.     

Ex vivo assessment of polyol coated-iron oxide nanoparticles for MRI diagnosis applications: toxicological and MRI contrast enhancement effects

Polyol synthesis is a promising method to obtain directly pharmaceutical grade colloidal dispersion of superparamagnetic iron oxide nanoparticles (SPIONs). Here, we study the biocompatibility and performance as T2-MRI contrast agents (CAs) of high quality magnetic colloidal dispersions (average hydrodynamic aggregate diameter of 16-27 nm) consisting of polyol-synthesized SPIONs (5 nm in mean particle size) coated with triethylene glycol (TEG) chains (TEG-SPIONs), which were subsequently functionalized to carboxyl-terminated meso-2-3-dimercaptosuccinic acid (DMSA) coated-iron oxide nanoparticles (DMSA-SPIONs). Standard MTT assays on HeLa, U87MG, and HepG2 cells revealed that colloidal dispersions of TEG-coated iron oxide nanoparticles did not induce any loss of cell viability after 3 days incubation with dose concentrations below 50 μg Fe/ml. However, after these nanoparticles were functionalized with DMSA molecules, an increase on their cytotoxicity was observed, so that particles bearing free terminal carboxyl groups on their surface were not cytotoxic only at low concentrations (<10 μg Fe/ml). Moreover, cell uptake assays on HeLa and U87MG and hemolysis tests have demonstrated that TEG-SPIONs and DMSA-SPIONs were well internalized by the cells and did not induce any adverse effect on the red blood cells at the tested concentrations. Finally, in vitro relaxivity measurements and post mortem MRI studies in mice indicated that both types of coated-iron oxide nanoparticles produced higher negative T2-MRI contrast enhancement than that measured for a similar commercial T2-MRI CAs consisting in dextran-coated ultra-small iron oxide nanoparticles (Ferumoxtran-10). In conclusion, the above attributes make both types of as synthesized coated-iron oxide nanoparticles, but especially DMSA-SPIONs, promising candidates as T2-MRI CAs for nanoparticle-enhanced MRI diagnosis applications.     

Discrepancy between different estimates of the hydrodynamic diameter of polymer-coated iron oxide nanoparticles in solution

We have synthesized iron oxide nanoparticles coated with a monolayer of dextran, with molecular weights of the polymer between 5 and 670 kDa. Transmission electron microscopy images confirm that the hard core has a crystalline diameter of approximately 12 nm. The hydrodynamic diameters of these coated nanoparticles in solution measured using dynamical light scattering and estimated from magnetic susceptibility studies vary from near 90 nm for the lightest polymer to 140 nm for the heaviest polymer. Conversely, fluorescence correlation spectroscopy measurements yield a diameter of approximately 55 nm for the 15?C20 kDa dextran coated nanoparticles, which is consistent with the expected value estimated from the sum of the hard-core diameter and monolayer dextran coating. We discuss the implications of this discrepancy for applications involving polymer-coated magnetic nanoparticles.     

White-light Detection for Nanoparticle Sizing with the TSI Ultrafine Condensation Particle Counter

Several of the most common methods for measuring nanoparticle size distributions employ the ultrafine condensation particle counter (UCPC) for detection purposes. Among these methods, the pulse height analysis (PHA) technique, in which the optical response of the UCPC detector is related to initial particle diameter in the 3–10nm range, prevails in applications where fast sampling is required or for which concentrations of nanoparticles are frequently very low. With the PHA technique, white light is required for particle illumination in order to obtain a monotonic relationship between initial particle diameter and optical response (pulse height). However, the popular, commercially available TSI Model 3025A UCPC employs a laser for particle detection. Here, we report on a novel white-light detection system developed for the 3025A UCPC that involves minimal alteration to the instrument and preserves normal counting operation. Performance is illustrated with pulse height spectra produced by differential mobility analyzer (DMA) – generated calibration aerosols in the 3–50nm range.     

A sonochemical synthesis of cyclodextrin functionalized Au-FeNPs for colorimetric detection of Cr6+ in different industrial waste water

This paper describes a simple, selective and sensitive colorimetric sensing of Cr⁶⁺ ions using β-Cyclodextrin (β-CD) functionalized gold-iron nanoparticles (β-CD/Au-FeNPs). The sonochemically synthesized nanoparticles are winered in colour due to the SPR band of β-CD functionalized bimetalic nanoparticles Au-FeNPs. The capping and stabilizing of Au-FeNPs by redox β-CD is confirmed by FT-IR. The particles are spherical in shape and it posses the effective diameter of 18–20 nm. Under optimized conditions, in the presence of Cr⁶⁺ the wine red Au-FeNPs solution was turned to colourless, accompanying the broadening and red shifting of SPR band. The ratio between the absorbance wavelength at 573 nm to 535 nm (A₅₇₃/A₅₃₅) is linearly correlated with the Cr⁶⁺ concentrations ranging from 50 nM to 500 nM, with a detection limit of Cr⁶⁺ of 2.5 nM was achieved for the first time using β-CD/Au-FeNPs by spectrophotometry. The selectivity of the β-CD/Au-FeNPs towards other interfering metal ions. Finally the proposed method has been successfully employed for the determination of Cr⁶⁺ ion in various industrial waste water with good recoveries.     

Gummic acid stabilized γ-Fe2O3 aqueous suspensions for biomedical applications

Biomedical applications of magnetic nanoparticles depend critically on their preparation as aqueous colloidal suspensions, or ferrofluids, with long term stability under physiological conditions. Dispersion of the magnetic nanoparticles is generally achieved by the use of protein cages, polysaccharide, polypeptide and charged macromolecular coatings, which minimize interparticle magnetic interactions, particle agglomeration and precipitation. The synthesis and characterization of gummic-acid stabilized maghemite ferrofluids is reported. X-ray diffraction, transmission electron microscope and dynamic light scattering measurements give a γ-Fe₂O₃ magnetic core diameter of 8 nm and a nanocomposite particle hydrodynamic diameter of 50 nm. Mössbauer and magnetization measurements indicate the presence of isolated, sterically stabilized superparamagnetic nanoparticles resistant to aging, and thus, promising agents for the production of novel magneto-pharmaceuticals.     

In vitro study of magnetic particle seeding for implant assisted-magnetic drug targeting

The concept of using magnetic particles (seeds) as the implant for implant assisted-magnetic drug targeting (IA-MDT) was analyzed in vitro. Since this MDT system is being explored for use in capillaries, a highly porous (ε∼70%), highly tortuous, cylindrical, polyethylene polymer was prepared to mimic capillary tissue, and the seeds (magnetite nanoparticles) were already fixed within. The well-dispersed seeds were used to enhance the capture of 0.87 μm diameter magnetic drug carrier particles (MDCPs) (polydivinylbenzene embedded with 24.8 wt% magnetite) under flow conditions typically found in capillary networks. The effects of the fluid velocity (0.015–0.15 cm/s), magnetic field strength (0.0–250 mT), porous polymer magnetite content (0–7 wt%) and MDCP concentration (C=5 and 50 mg/L) on the capture efficiency (CE) of the MDCPs were studied. In all cases, when the magnetic field was applied, compared to when it was not, large increases in CE resulted; the CE increased even further when the magnetite seeds were present. The CE increased with increases in the magnetic field strength, porous polymer magnetite content and MDCP concentration. It decreased only with increases in the fluid velocity. Large magnetic field strengths were not necessary to induce MDCP capture by the seeds. A few hundred mT was sufficient. Overall, this first in vitro study of the magnetic seeding concept for IA-MDT was very encouraging, because it proved that magnetic particle seeds could serve as an effective implant for MDT systems, especially under conditions found in capillaries.     

Catalytic synthesis and photoluminescence of silicon oxide nanowires and nanotubes

A large quantity of nanowires and nanotubes of silicon oxide are produced by using Fe–Co–Ni alloy nanoparticles as catalyst. The products have a uniform diameter of around 100 nm. The nanowires have a smooth surface and the lengths are up to 100 μm or more. A new morphology called a serrated joint nanotube was found. The alloy catalyst plays a key role in the synthesis process. Room-temperature photoluminescence measurement under excitation at 360 nm showed that the silicon oxide had a strong blue-green emission at 525 nm (about 2.36 eV), which may be related to oxygen defects. PACS 81.15.Gh; 81.07.Vb; 81.07.De; 42.70.Nq; 78.55.-m     

DNA分析仪的灵敏度分析

设计了DNA分析仪,采用激光诱导荧光对样品的毛细管电泳结果进行检测,对仪器的灵敏度进行了理论分析和实验测试.分析表明:荧光的探测灵敏度取决于入射到光探测器(PMT或CCD)上的荧光强度及光探测器自身的探测能力.结合设计参量,计算得到DNA分析仪针对染料TO(thiazole orange)作为荧光标记的探测灵敏度为0.127 fluor/μm3个荧光分子.和实验结果相比,双链DNA样品pGEM-3Zf(+)/Hae III Markers加TO进行毛细管电泳实验,得到实际的探测灵敏度为0.145 4 fluor/μm3荧光分子.研究表明:提高探测灵敏度的措施是制备性能良好的毛细管涂层和合理使用筛分介质,合理增大激光功率、尽可能增大物镜的数值孔径、提高光电倍增管的探测下限.     

Cyclodextrin-conjugated nanocarrier for magnetically guided delivery of hydrophobic drugs

A magnetic nanosystem that simultaneously implements the cyclodextrin–drug complexation power, bioadhesive property of gum arabic (GA) and inherent magnetic properties of Fe₃O₄ nanoparticles, has recently been reported. In this study, a magnetic nanocarrier was fabricated by conjugating 2-hydroxypropyl-cyclodextrin (HCD) onto the gum arabic modified magnetic nanoparticles (GAMNP). The analyses of transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the product had a mean diameter of 14.8 nm and a mean hydrodynamic diameter of 29.3 nm. This nanocarrier showed good loading efficiency for ketoprofen. In addition, the in vitro release profile of ketoprofen from HCD-GAMNP was characterized by an initial fast release followed by a delayed release phase. In view of the better biocompatibility and the combined properties like specific targeting, complexation ability with hydrophobic drugs makes the nanosystem an exciting prospect for drug delivery.     

Homogeneous ZnO Nanoparticles by Flame Spray Pyrolysis

Zinc oxide (ZnO) nanoparticles were made by flame spray pyrolysis (FSP) of zinc acrylate–methanol–acetic acid solution. The effect of solution feed rate on particle specific surface area (SSA) and crystalline size was examined. The average primary particle diameter can be controlled from 10 to 20nm by the solution feed rate. All powders were crystalline zincite. The primary particle diameter observed by transmission electron microscopy (TEM) was in agreement with the equivalent average primary particle diameter calculated from the SSA as well as with the crystalline size calculated from the X-ray diffraction (XRD) patterns for all powders, indicating that the primary particles were rather uniform in diameter and single crystals. Increasing the solution feed rate increases the flame height, and therefore coalescence and/or surface growth was enhanced, resulting in larger primary particles. Compared with ZnO nanoparticles made by other processes, the FSP-made powder exhibits some of the smallest and most homogeneous primary particles. Furthermore, the FSP-made powder has comparable BET equivalent primary particle diameter with but higher crystallinity than sol–gel derived ZnO powders.     

Simultaneous laser-induced fluorescence and sub-Doppler polarization spectroscopy of the CH radical

The first application of polarization spectroscopy (PS) to the CH radical is demonstrated. In particular, we report on the simultaneous application of laser-induced fluorescence (LIF) and sub-Doppler PS to CH. The conventional experimental setup for PS was supplemented with a second detection system in order to collect the LIF emission. At the same time a Fabry–Perot etalon and molecular iodine were utilized to obtain a precise relative and absolute frequency scale, respectively. CH was investigated in a low pressure methane–oxygen flame. The R₂(5) transition of the B–X (0, 0) band corresponding to a wavelength around 387.3 nm was scanned while fluorescence emission was collected in the spectral region around 431 nm from the B–X (0, 1), A–X (1, 1) and A–X (0, 0) bands. The saturation behavior of both techniques is investigated as well as line broadening effects due to the pump laser pulse energy or rather fluence. Saturation fluence for LIF was found to be more than one order of magnitude higher as compared to PS.     

Application of calixarene to high active surface‐enhanced Raman scattering (SERS) substrates suitable for in situ detection of polycyclic aromatic hydrocarbons (PAHs) in seawater

The characteristics of the sol–gel matrix embedding Ag nanoparticles functionalized with 25,27‐dimercaptoacetic acid‐26,28‐dihydroxy‐4‐tert‐butylcalix[4]arene (DMCX) suitable for the in situ detection of polycyclic aromatic hydrocarbons (PAHs) in seawater is presented. The DMCX‐functionalized silver nanoparticles were produced by the thermal reduction method in xerogel film. The silver colloid blocks were formed in the sol–gel matrix, with a diameter ranging from 50 to 120 nm. DMCX forming the monolayer on the silver nanoparticle surface contributes to the surface‐enhanced Raman scattering (SERS) activity due to the aggregation of silver nanoparticles and the preconcentration of PAH molecules within the zone of electromagnetic enhancement. When selected, PAH molecules e.g. pyrene and naphthalene were adsorbed onto the SERS substrate; Raman band positions of PAH were slightly shifted. A calibration procedure reveals that this type of SERS substrate has a limit of detection of 3 × 10⁻¹⁰ mol/l for pyrene and 13 × 10⁻⁹ mol/l for naphthalene in artificial seawater. The Raman signal response on a pyrene concentration change in artificial seawater was evaluated using a 671‐nm Raman setup with a flow‐through cell. This type of SERS substrate will be suitable for the in situ trace detection of pollutant chemicals in seawater. Copyright © 2012 John Wiley & Sons, Ltd.     

Deviations from Bloch law in the case of surfacted nanoparticles

Bloch’s law which describes the variation with temperature of the spontaneous magnetization at low temperatures no longer applies in the case of surfacted nanoparticles. The deviation is a result of the modification of the superexchange interaction in the surface layer of the nanoparticles, which leads to an increase of the magnetic diameter (D_m) (attached to the core where the spins are ferrimagnetically aligned), and of their magnetic moment, when the temperature decreases below 300 K. This anomaly was studied for a ferrofluid containing particles of Mn_0.6Fe_2.4O₄ with a mean physical diameter of 〈D〉=12.2 nm that were surfacted with oleic acid. Taking into account the contribution of the layer at the nanoparticles’ surface, based on experimental results I have established the law for the variation of the saturation magnetization (M_sat(T)) with temperature (T) in this case as an addendum to the Bloch law. The temperature dependence of χ_i^-1 (χ_i – initial susceptibility) of the nanoparticle system in the range T>T_b (T_b – blocking temperature), confirms on the one hand, the increase of the nanoparticles’ magnetic diameter when they cool down, and on the other hand, confirms the law that I have found for the dependence M_sat(T). PACS 75.30.Cr; 75.30.Pd; 75.50.Tt     

Preparation of Gold/triblock Copolymer Composite Nanoparticles

A kind of novel gold (Au)/hydroxylated poly (styrene-b-butadiene-b-styrene) triblock copolymer (HO-SBS) composite nanoparticles was synthesized by reduction of tetrachloroaurate ions in HO-SBS micelle. The Au–HO-SBS composite nanoparticles are composed by gold core about 35 nm in diameter and polymer shell about 7 nm in thickness. Formation of the Au/HO-SBS nanoparticles is indentified by infrared (IR) and UV-visible absorption spectroscopies. Transmission electron microscopy (TEM) result shows that the composite nanoparticles tend to aggregate into an ordered hexagonal array on carbon-coated grid.     

Electrical and magnetic properties of polyaniline/Fe3O4 nanostructures

We report on electrical and magnetic properties of polyaniline (PANI) nanotubes (150 nm in diameter) and PANI/Fe₃O₄ nanowires (140 nm in diameter) containing Fe₃O₄ nanoparticles with a typical size of 12 nm. These systems were prepared by a template-free method. The conductivity of the nanostructures is 10⁻¹–10⁻² S/cm; and the temperature dependent resistivity follows a ln ρT^−1/2 law. The composites (6 and 20 wt% of Fe₃O₄) show a large negative magnetoresistance compared with that of pure PANI nanotubes and a considerably lower saturated magnetization (M_s=3.45 emu/g at 300 K and 4.21 emu/g at 4 K) compared with the values measured from bulk magnetite (M_s=84 emu/g) and pure Fe₃O₄ nanoparticles (M_s=65 emu/g). AC magnetic susceptibility was also measured. It is found that the peak position of the AC susceptibility of the nanocomposites shifts to a higher temperature (>245 K) compared with that of pure Fe₃O₄ nanoparticles (190–200 K). These results suggest that interactions between the polymer matrix and nanoparticles take place in these nanocomposites.