Nitric oxide donor superparamagnetic iron oxide nanoparticles

This work reports a new strategy for delivering nitric oxide (NO), based on magnetic nanoparticles (MNPs), with great potential for biomedical applications. Water-soluble magnetic nanoparticles were prepared through a co-precipitation method by using ferrous and ferric chlorides in acidic solution, followed by a mercaptosuccinic acid (MSA) coating. The thiolated nanoparticles (SH-NPs) were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). The results showed that the SH-NPs have a mean diameter of 10 nm and display superparamagnetic behavior at room temperature. Free thiol groups on the magnetite surface were nitrosated through the addition of an acidified nitrite solution, yielding nitrosated magnetic nanoparticles (SNO-NPs). The amount of NO covalently bound to the nanoparticles surface was evaluated by chemiluminescense. The SNO-NPs spontaneously released NO in aqueous solution at levels required for biomedical applications. This new magnetic NO-delivery vehicle has a great potential to generate desired amounts of NO directed to the target location.     

Characterization of superparamagnetic iron oxide nanoparticles and its application in protein purification

The application of surface modified magnetic adsorbent particles in combination with magnetic separation techniques has received considerable awareness in recent years. There is a particular need in protein purification and analysis for specific, functional and generic methods of protein binding on solid supports. Nanoscale superparamagnetic iron oxide particles have been used to purify a natural coagulant protein extracted from Moringa oleifera seeds. Spectrophotometric analysis of the coagulant protein was performed using synthetic clay solution as substrate. Protein binding with carboxyl and silica surface modified superparamagnetic iron oxide nanoparticles (SPION) were compared with the known carboxyl methyl cellulose (CMC) beads of approximately 1 microm. SPION modified with carboxyl surface showed higher binding capacity towards the coagulant protein compared to the CMC beads. The high surface area to volume ratio of the carboxyl-coated SPION resulted in high binding capacity and rapid adsorption kinetics of the crude protein extract. The purification and molecular weight of coagulant protein is analyzed by SDS-PAGE. This approach utilizes the most efficient, feasible and economical method of coagulant protein purification and it can also be applicable to other proteins that possess similar properties.     

Antioxidant efficacy of chitosan/graphene functionalized superparamagnetic iron oxide nanoparticles

The antioxidant potential of superparamagnetic iron oxide nanoparticles functionalized with chitosan and graphene were examined in the present work. Coprecipitation technique was followed for the synthesis of iron oxide nanoparticles. Graphene-iron oxide nanocomposites were synthesized by mechanical mixing followed by the heat treatment at moderate temperature. The chitosan coated iron oxide nanoparticles were prepared by dispersing nanoparticles in chitosan solution. The nanoparticles/nanocomposites were characterized using XRD, SEM, TEM and HAADF-STEM for phase structure, morphology and elemental analysis. The superparamagnetic behavior of nanoparticles/nanocomposites were confirmed by magnetic measurements using vibrating sample magnetometry. Antioxidant efficacy of these nanoparticles/nanocomposites were investigated in terms of free radical scavenging and reducing potential using an array of in vitro assay system. Ferric reducing antioxidant power (FRAP) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) were used for the antioxidant capacity. The investigation suggests that the graphene improves the antiradical response of iron oxide nanoparticles at higher concentration which is almost comparable to the ascorbic acid used as standard.     

Adsorption of Cd2+ on carboxyl-terminated superparamagnetic iron oxide nanoparticles

The affinity of Cd(2+) toward carboxyl-terminated species covalently bound to monodisperse superparamagnetic iron oxide nanoparticles, Fe(3)O(4)(np)-COOH, was investigated in situ in aqueous electrolytes using rotating disk electrode techniques. Strong evidence that the presence of dispersed Fe(3)O(4)(np)-COOH does not affect the diffusion limiting currents was obtained using negatively and positively charged redox active species in buffered aqueous media (pH = 7) devoid of Cd(2+). This finding made it possible to determine the concentration of unbound Cd(2+) in solutions containing dispersed Fe(3)O(4)(np)-COOH, 8 and 17 nm in diameter, directly from the Levich equation. The results obtained yielded Cd(2+) adsorption efficiencies of ~20 μg of Cd/mg of Fe(3)O(4)(np)-COOH, which are among the highest reported in the literature employing ex situ methods. Desorption of Cd(2+) from Fe(3)O(4)(np)-COOH, as monitored by the same forced convection method, could be accomplished by lowering the pH, a process found to be highly reversible.     

A simple synthesis of amine-derivatised superparamagnetic iron oxide nanoparticles for bioapplications

Adsorption of 3-aminopropyltriethoxysilane (APTS) on magnetite nanoparticles during its formation has been investigated to optimise the preparation of stable aqueous dispersion of amine derivatised magnetite nanoparticles. APTS adsorbs chemically on the surface of magnetite particle modifying its surface which is evident from thermal and C, H, N analysis. The variation of particle size has been observed with change of APTS concentration. X-ray diffractogram shows the formation of pure inverse spinel phase magnetite with average crystallite size 7 nm when equimolar (Fe₃O₄: APTS = 1:1) quantity of APTS was used during its synthesis. The presence of free surface –NH₂ groups and Fe–O–Si bonds was observed by FTIR. Raman spectrum further confirms the presence of surface –NH₂ groups. Transmission electron microscopy shows formation of particles of average size between 7 nm and 12 nm. The effective hydrodynamic diameter of the APTS coated particle agglomerates is 45.8 nm in stable aqueous colloidal dispersion, which is evident from photon correlation spectroscopy. VSM measurements at room temperature of both silanised and unsilanised magnetite shows their superparamagnetic nature with saturation magnetisation 41 e.m.u/g and 56 e.m.u/g, respectively. Avidin has been immobilised on the surface through glutaraldehyde, which demonstrates the possibility of the synthesised material to be used in protein immobilisation to form bioactive magnetic particles.     

Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity

We describe a new method for coating superparamagnetic iron oxide nanoparticles (SPIOs) and demonstrate that, by fine-tuning the core size and PEG coating of SPIOs, the T2 relaxivity per particle can be increased by >200-fold. With 14 nm core and PEG1000 coating, SPIOs can have T2 relaxivity of 385 s-1 mM-1, which is among the highest per-Fe atom relaxivities. In vivo tumor imaging results demonstrated the potential of the SPIOs for clinical applications.     

Image-guided prostate cancer therapy using aptamer-functionalized thermally cross-linked superparamagnetic iron oxide nanoparticles

CG-rich duplex containing prostate-specific membrane antigen (PSMA) aptamer-conjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPIONs) is reported as prostate cancer-specific nanotheranostic agents. These agents are capable of prostate tumor detection in vivo by magnetic resonance imaging (MRI) and selective delivery of drugs to the tumor tissue, simultaneously. The prepared PSMA-functionalized TCL-SPION via a hybridization method (Apt-hybr-TCL-SPION) exhibited preferential binding towards target prostate-cancer cells (LNCaP, PSMA+) in both in vitro and in vivo when analyzed by T(2) -weighted MRI. After Dox molecules were loaded onto the Apt-hybr-TCL-SPION through the intercalation of Dox to the CG-rich duplex containing PSMA aptamer as well as electrostatic interaction between the Dox-and-polymer coating layer of the nanoparticles, the resulting Dox@Apt-hybr-TCL-SPION showed selective drug-delivery efficacy in the LNCaP xenograft mouse model. These results suggest that Dox@Apt-hybr-TCL-SPION has potential for use as novel prostate cancer-specific nanotheranostics.     

Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

LHRH-functionalized superparamagnetic iron oxide nanoparticles for breast cancer targeting and contrast enhancement in MRI

This paper shows that superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to luteinizing hormone releasing hormone (LHRH) (LHRH–SPIONs), can be used to target breast cancer cells. They also act as contrast enhancement agents during the magnetic resonance imaging of breast cancer xenografts. A combination of transmission electron microscopy (TEM) and spectrophotometric analysis was used in our experiments, to investigate the specific accumulation of the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) in cancer cells. The contrast enhancement of conventional T2 images obtained from the tumor tissue and of breast cancer xenograft bearing mice is shown to be much greater than that in saline controls, when the tissues were injected with LHRH–SPIONs. Magnetic anisotropy multi-CRAZED images of tissues extracted from mice injected with SPIONs were also found to have enhanced MRI contrast in breast cancer xenografts and metastases in the lungs.     

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。     

Encapsulation of superparamagnetic iron oxide nanoparticles in poly-(lactide-co-glycolic acid) microspheres for biomedical applications

Magnetic microspheres were prepared using a single step coaxial electrohydrodynamic atomization technique at ambient temperature and pressure, with poly(lactic-co-glycolic acid) as the coating and iron oxide (Fe₃O₄) nanoparticles dispersed in polyethylene glycol as the encapsulated material. The morphology and particle size distributions of the prepared magnetic microspheres were investigated by scanning electron microscopy. The particles were spherical with mean diameters ranging from ~ 2 μm to 18 μm, depending on the combination of processing parameters (flow rate and applied voltage). Analysis by infrared spectroscopy and focused ion-beam sectioning confirmed incorporation of iron oxide nanoparticles into the microspheres and the prepared samples were shown to be responsive to an applied magnetic field. This study demonstrates a convenient method for the preparation of nanoparticle loaded microspheres, which could be used potentially as transverse relaxation contrast agents in magnetic resonance imaging, as well as for magnetically guided drug delivery.     

Dextran coated ultrafine superparamagnetic iron oxide nanoparticles: compatibility with common fluorometric and colorimetric dyes

Due to the unique physicochemical properties of nanomaterials (NM) and their unknown reactivity, the possibility of NM altering the optical properties of fluorometric/colorimetric probes that are used to measure their cyto- and genotoxicity may lead to inaccurate readings. This could have potential implications given that NM, such as ultrafine superparamagnetic iron oxide nanoparticles (USPION), are increasingly finding their use in nanomedicine and the absorbance/fluorescence based assays are used to assess their toxicity. This study looks at the potential of dextran-coated USPION (dUSPION) (maghemite and magnetite) to alter the background signal of common probes used for evaluating cytotoxicity (MTS, CyQUANT, Calcein, and EthD-1) and oxidative stress (DCFH-DA and APF). In the present study, both forms of dUSPION caused an increase in MTS signal but a decrease in background signal from calcein and 3'-(p-aminophenyl) fluorescein (APF) and no effect on CyQUANT and EthD-1 fluorescence responses. Magnetite caused a decrease in fluorescence signal of DCFH, but it did not decrease fluorescence signal in the presence of the reactive oxygen species-inducer tert-butyl hydroperoxide (TBHP). In contrast, maghemite caused an increase in fluorescence, which was substantially reduced in the presence of the antioxidant N-acetyl cysteine. This study emphasizes the importance of considering and controlling for possible interactions between NM and fluorometric/colorimetric dyes and, most importantly, the oxidation state of dUSPION that may confound their sensitivity and specificity.     

Surface modified superparamagnetic iron oxide nanoparticles: as a new carrier for bio-magnetically targeted therapy

Amino-functionalized superparamagnetic iron oxide nanoparticles (SPION) were synthesized by coprecipitation method. The particles were characterized by X-ray diffraction (XRD), vibrating sample magnetometer (VSM), scanning electron micrographs (SEM), transmission electron micrographs (TEM) and atomic force micrographs (AFM). The size of the modified particles varied in the range 10–15 nm and did not change significantly after modification. Hepama-1, an excellent humanized monoclonal antibody directed against liver cancer, was conjugated to the SPION to prepare immuno-magnetic nanoparticles (IMN). A direct labeling method was employed to radiolabel IMN with rhenium-188. The radiolabeling efficiency was about 90% with good in vitro stability. ¹⁸⁸Re labeled IMN could markedly kill SMMC-7721 liver cancer cells. Such SPION might be very useful for bio-magnetically targeted radiotherapy in liver cancer treatment.     

Controlled aggregation of superparamagnetic iron oxide nanoparticles for the development of molecular magnetic resonance imaging probes

A method for synthesizing superparamagnetic iron oxide (SPIO) multi-nanoparticle aggregates as molecular magnetic resonance imaging (MRI) contrast agents is described. The approach utilizes organic acid/base interactions in the colloid to induce highly controllable nanoparticle aggregation. Monodisperse aggregates with diameters as large as 100?nm are synthesized by manipulating the interfacial surface chemistry of the SPIO nanoparticles in tetrahydrofuran solvent. Subsequent phospholipid micelle encapsulation yields micellar multi-SPIO (mmSPIO) aggregates with enhanced T(2) relaxivity (368.0?s(-1)?mmol(-1)?Fe) as compared to micellar single particle SPIO (302.0?s(-1)?mmol(-1)?Fe). mmSPIO conjugated to anti-CA125 monoclonal antibodies were incubated with ovarian carcinoma cell lines to demonstrate targeted in vitro molecular MRI, resulting in a?66% shortening in T(2) time for CA125 positive NIH:OVCAR-3 cells and a less than?3% change in T(2) time for CA125 negative SK-OV-3 cells. The controllable aggregation of mmSPIO shows potential for the development of molecular MRI contrast agents with optimal sizes for specific diagnostic imaging applications.     

Surface ligand influenced free radical protection of superparamagnetic iron oxide nanoparticles (SPIONs) toward H9c2 cardiac cells

There have been a number of studies which deal with either toxic or non-toxic nature of superparamagnetic iron oxide nanoparticles (SPIONs); however, there is no clear cut information about their exact behavior and the reasons for its dual action. The objective of the present study was to investigate the SPIONs having similar oxidation states, but varying surface ligands and their role in terms of protecting the iron-mediated toxic responses. The four different SPIONs includes: (i) SPIONs containing oleic acid (SPIONs-1), (ii) SPIONs without any surface ligand (SPIONs-2), (iii) SPIONs containing cysteamine ligand (SPIONs-3), and (iv) SPIONs having both of oleic acid and cysteamine ligand. The particle size, surface functionality, and electronic oxidation states were confirmed by the HRTEM, FT-IR, and XPS analysis, respectively. On in vitro testing of all four SPIONs with H9c2 cardiomyocyte cell line, the SPIONs-2 without any surface ligand found to exhibit significant decrease in the viability of cells at a concentration of 200 μg mL^?1 for 16-h exposure period. Further investigation of toxicity mechanism resulted in the fact that the SPIONs-2 involved in the formation of ROS due to the role played by the more electron deficient Fe³⁺ form of iron, there by decreased the glutathione release, increased DNA cleavage, and disrupted the mitochondrial transmembrane potential. However, the presence of unsaturation and/or thiol group (–SH) containing ligands on other SPIONs protected the cardiac cells from undergoing ROS-induced oxidative stress. Further, the results of the study confirming the importance of having unsaturated double bonds and/or –SH group possessing ligands onto the surface of SPIONs by means of protecting the cells from the influence of electron deficient Fe³⁺ state of iron.     

Highly water-dispersible PEG surface modified ultra small superparamagnetic iron oxide nanoparticles useful for target-specific biomedical applications

For the application of superparamagnetic iron oxide nanoparticles in biomedical fields for target-specific purposes, they should be ultra small in diameter. We developed a simple one-step synthesis of surface modified ultra small superparamagnetic iron oxide nanoparticles (USPIONs) with an average particle diameter of 1.7?nm in a polar organic solvent. Polyethylene glycol diacid (PEG) surface modified USPIONs synthesized in triethylene glycol were nearly monodisperse in diameter and highly water-dispersible. The PEG surface modified USPIONs were tested for use as magnetic resonance (MR) contrast agents. They had a low r(2)/r(1) relaxivity ratio of 3.4 (r(1) = 4.46 and r(2) = 15.01?mM(-1)?s(-1)) and showed clear dose-dependent T(1) and T(2) map images, indicating that they will be useful as both target-specific T(1) and T(2) MR contrast agents due to their ultra small size.     

Multifunctional iron and iron oxide nanoparticles in silica

Iron and iron oxide nanoparticles in silica layers deposited by sol–gel techniques on Si wafers were formed and studied. It was shown that multifunctional nanoparticles of different iron oxides possessing various physical properties can be fabricated by means of post-growth annealing of (SiO₂:Fe)/SiO₂/Si samples in various atmospheres. The hematite, maghemite, and iron nanoparticles were found to be dominant upon annealing the samples in air, argon, and hydrogen atmosphere, respectively. The physical properties of produced hybrid structures were studied by Raman and FT-IR spectroscopy, spectroscopic ellipsometry, AFM, and magnetic measurements. The sol–gel technique with subsequent annealing procedure is demonstrated to be an effective method for the formation of multifunctional hybrid structures composed of iron or iron oxide nanoparticles in silica matrix.     

Templated growth of superparamagnetic iron oxide nanoparticles by temperature programming in the presence of poly(vinyl alcohol)

Magnetite (Fe₃O₄) nanostructures with different morphologies including uniform nanoparticles, magnetic beads and nanorods were synthesized via a co-precipitation method. The synthesis process was performed at various temperatures in the presence of polyvinyl alcohol (PVA) at different concentrations. It is shown that small amounts of PVA act as a template in hot water (70 °C), leading to the oriented growth of Fe₃O₄ nanorods, which was confirmed by selected area electron diffraction. Individually coated magnetite nanoparticles and magnetic beads were formed at a relatively lower temperature of 30 °C in the folded polymer molecules due to the thermo-physical properties of PVA. When a moderate temperature (i.e. 50 °C) was used, nanorods and nanobeads co-existed. At higher concentrations of PVA (polymer/iron mass ratio of 5), however, the formation of magnetic beads was favored. The nanorods were shown to be unstable upon exposure to electron beams. Freezing/thawing process was applied post synthesis as temperature programming to fabricate stable nanorods with rigid walls.     

Seed-mediated synthesis of iron oxide and gold/iron oxide nanoparticles

In this study, we prepared magnetic iron oxide and gold/iron oxide nanoparticles (NPs) and characterized their morphologies and properties by XRD, TEM, EDX, VSM and UV-vis measurements. The magnetite iron oxide NPs of 10 nm were synthesized by coprecipitation of Fe2+ and Fe+3 in the solution of NH4OH and then they were used as seed particles for the subsequent growth to prepare the magnetite NPs of different particle sizes and also to prepare gold/iron oxide composite NPs. All those magnetite NPs are superparamagnetic and the gold/iron oxide composite NPs combine the optical and magnetic properties, which are contributed by gold and iron oxide components, respectively.     

Enhanced bio-compatibility of ferrofluids of self-assembled superparamagnetic iron oxide-silica core-shell nanoparticles

Self-assembled magnetic colloidal suspensions are sought after by material scientists owing to its huge application potential. The biomedical applications of colloidal nanoparticles necessitate that they are biocompatible, non-interacting, monodispersed and hence the synthesis of such nanostructures has great relevance in the realm of nanoscience. Silica-coated superparamagnetic iron oxide nanoparticles based ferrofluids were prepared using polyethylene glycol as carrier fluid by employing a controlled co-precipitation technique followed by a modified sol-gel synthesis. A plausible mechanism for the formation of stable suspension of SiO2-coated Iron Oxide nanoparticles with a size of about 9 nm dispersed in polyethylene glycol (PEG) is proposed. Core-shell nature of the resultant SiO2-Iron Oxide nanocomposite was verified using transmission electron microscopy. Fourier transform-infrared spectroscopy studies were carried out to understand the structure and nature of chemical bonds. The result suggests that Iron Oxide exist in an isolated state inside silica matrix. Moreover, the presence of silanol bonds establishes the hydrophilic nature of silica shell confirming the formation of stable ferrofluid with PEG as carrier fluid. The magnetic characterization reveals the superparamagnetic behavior of the nanoparticles with a rather narrow distribution of blocking temperatures. These properties are not seen in ferrofluids prepared from Iron Oxide nanoparticles without SiO2 coating. The latter suggests the successful tuning of the inter-particle interactions preventing agglomeration of nanoparticles. Cytotoxicity studies on citric acid coated water based ferrofluid and silica-coated PEG-based ferrofluid were evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium chloride assay and it shows an enhanced compatibility for silica modified nanoparticles.