Recent Progress in Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles(SPIONs)have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size.This review introduces the methods for SPIONs synthesis,including co-precipitation,thermal decomposition,microemulsion and hydrothermal reaction,and surface modification of SPIONs with organometallic and inorganic metals,surface modification for targeted drug delivery,and the use of SPIONs as a contrast agent.In addition,this article also provides an overview of recent progress in SPIONs for the treatment of glioma,lung cancer and breast cancer.

Highly Efficient Labeling of Human Lung Cancer Cells Using Cationic Poly-L-lysine-Assisted Magnetic Iron Oxide Nanoparticles

Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.

Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo

Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.

Green synthesis of iron oxide(Fe_3O_4)nanoparticles using two selected brown seaweeds:Characterization and application for lead bioremediation

The exploitation of different plant materials for the biosynthesis of nanoparticles is considered a green technology because it does not involve any harmful chemicals. In this study, iron oxide nanoparticles（Fe3O4-NPs） were synthesized using a completely green biosynthetic method by reduction of ferric chloride solution using brown seaweed water extracts. The two seaweeds Padina pavonica（Linnaeus） Thivy and Sargassum acinarium（Linnaeus） Setchell 1933 were used in this study. The algae extract was used as a reductant of Fe Cl3 resulting in the phytosynthesis of Fe3O4-NPs. The phytogenic Fe3O4-NPs were characterized by surface plasmon band observed close to 402 nm and 415 nm; the obtained Fe3O4-NPs are in the particle sizes ranged from 10 to 19.5 nm and 21.6 to 27.4 nm for P. pavonica and S. acinarium, respectively. The strong signals of iron were reported in their corresponding EDX spectra. FTIR analyses revealed that sulphated polysaccharides are the main biomolecules in the algae extracts that do dual function of reducing the Fe Cl3 and stabilizing the phytogenic Fe3O4-NPs. The biosynthesized Fe3O4-NPs were entrapped in calcium alginates beads and used in Pb adsorption experiments. The biosynthesized Fe3O4-NPs alginate beads via P. pavonica（Linnaeus） Thivy had high capacity for bioremoval of Pb（91%） while that of S. acinarium（Linnaeus） Setchell 1933 had a capacity of（78%） after 75 min.The values of the process parameters for the maximum Pb removal efficiency by Fe3O4-NPs alginate beads synthesized via P. pavonica（Linnaeus） Thivy were also estimated.

Use of PEI-coated Magnetic Iron Oxide Nanoparticles as Gene Vectors

Summary: To evaluate the feasibility of using polyethyleneimine (PEI) coated magnetic iron oxide nanoparticles (polyMAG-1000) as gene vectors. The surface characteristics of the nanoparticles were observed with scanning electron microscopy. The ability of the nanoparticles to combine with and protect DNA was investigated at different PH values after polyMAG-1000 and DNA were combined in different ratios. The nanoparticles were tested as gene vectors with in vitro transfection models. Under the scanning electron microscope the nanoparticles were about 100 nm in diameter. The nanoparticles could bind and condense DNA under acid, neutral and alkaline conditions, and they could transfer genes into cells and express green fluorescent proteins (GFP). The transfection efficiency was highest (51 %) when the ratio of nanoparticles to DNA was 1:1 (v:w). In that ratio, the difference in transfection efficiency was marked depending on whether a magnetic field was present or not: about 10 % when it was absent but 51 % when it was present. The magnetic iron oxide nanoparticles coated with PEI may potentially be used as gene vectors.

Toxicity of superparamagnetic iron oxide nanoparticles: Research strategies and implications for nanomedicine

Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.

Water oxidation electrocatalysis with iron oxide nanoparticles prepared via laser ablation

Iron oxide nanoparticles（FeOx NPs, 5–30 nm size） prepared via laser ablation in liquid were supported onto Indium Tin Oxide conductive glass slides by magnetophoretic deposition（MD） technique. The resulting Fe O x@ITO electrodes are characterized by a low amount of iron coverage of 16–50 nmol/cm^2,and show electrocatalytic activity towards water oxidation in neutral phosphate buffer pH 7 with 0.58 V overpotential and quantitative Faradaic efficiency towards oxygen production. XPS analysis on the oxygen region of the FeOx films reveals a substantial hydration of the surface after catalysis, recognized as a crucial step to access reactivity.

Adsorption of Propazine, Simazine and Bisphenol A on the Surface of Nanoparticles of Iron Oxide Nanoparticles of Carbon and Metallic Oxides

Simazine and propazine are selective triazine herbicides currently in use to control broad-leaved weeds and annual grasses around the world. Bisphenol A (BPA) is an industrial chemical used in the production of polycarbonate plastics often found in consumer goods, such as plastic containers, baby bottles etc. These synthetic compounds are known to increase the risk of cancer, cause adverse reproductive effect in reptiles, mammals, birds, humans, and lead to other health problems. They have become some of the principal agents of contamination in water bodies around the world through herbicide runoff, industrial waste and leaching. Some triazines such as atrazine are banned in most European countries for over ten years due to their adverse reproductive effect in mammals, birds and humans;however propazine and simazine are still in use around the world. The removal of these compounds from contaminated water is an exigent challenge. In this study, we investigated their affinity for the surface of nanoparticles (NPS) and standard metallic oxides in an effort to exploit the unique potential applications of NPS for water purification systems. We studied the adsorption of the two triazines and BPA on the surface of NPS of iron (III) oxide, NPS of carbon, bulk iron (III) oxide and aluminum oxide at pH 6 and pH 8 using UV-Visible spectroscopy. Result indicates that these compounds have different affinity towards the surface of metallic oxides and carbon at various pHs. In general, there is relatively high adsorption of some of these compounds on the surface of NPS compared to bulk particles. NPS of carbon have shown the highest affinity for all the three compounds. The lower pH was found to be favorable for all of the compounds except for BPA. BPA have shown high adsorption at pH 8 than at pH 6.

Iron Oxide Nanoparticles Induced Oxidative Damage in Peripheral Blood Cells of Rat

Nanotechnology is a rapidly growing field that has elicited much concern due to a variety of applications in different fields such as industry, medicine, and cosmetics. These developments increase the concern among the general population. Hence, there is an urgent need to explore the possible human health effects of these nanomaterials. The present study is aimed to evaluate the cytotoxic and genotoxic effects of iron oxide nanoparticles (IONPs) in-vivo. In order to study the toxic effects, Wistar rats were administered intravenously with various doses of IONPs (Fe2O3) through caudal vein once in a week for 28 days, and various biochemical assays such as antioxidant enzymes activity (SOD, CAT, and GSH), lipid peroxidation, DNA damage and hematological parameters were evaluated. Genotoxicity was evaluated by comet assay and oxidative stress was measured by anti-oxidant enzymes. The results reveal that IONPs alter hematological factor such as RBC counts, WBC counts, neutrophils, monocytes and hemoglobin. A dose-dependent inhibition (p < 0.05) of antioxidant enzymes was found, and meanwhile the level of MDA elevated significantly (p < 0.05) in IONPs treated groups in dose-dependent manner;however comet assay results indicate that IONPs did not induce any significant DNA damage. The present study concluded that IONP affects inflammatory response, which induces the oxidative stress and may adversely affect the cellular function.

Bovine Serum Albumin-Conjugated Ferrimagnetic Iron Oxide Nanoparticles to Enhance the Biocompatibility and Magnetic Hyperthermia Performance

Magnetic hyperthermia is a fast emerging, non-invasive cancer treatment method which is used synergistically with the existing cancer therapeutics. We have attempted to address the current challenges in clinical magnetic hyperthermia-improved biocompatibility and enhanced heating characteristics, through a single combinatorial approach. Both superparamagnetic iron oxide nanoparticles(SPIONs) of size 10 nm and ferrimagnetic iron oxide nanoparticles(FIONs) of size 30 nm were synthesized by thermal decomposition method for comparison studies. Two different surface modifying agents, viz, Cetyl Trimethyl Ammonium Bromide and 3-Aminopropyltrimethoxysilane, were used to conjugate Bovine Serum Albumin(BSA) over the iron oxide nanoparticles via two different methods—surface charge adsorption and covalent amide bonding, respectively. The preliminary haemolysis and cell viability experiments show that BSA conjugation mitigates the haemolytic effect of the iron oxide nanoparticles on erythrocytes and is non-cytotoxic to the healthy Baby Hamster Kidney cells. It was observed from the results that due to better colloidal stability, the SAR value of the BSA-iron oxide nanoparticles is higher than the iron oxide nanoparticles without BSA, irrespective of the size of the iron oxide nanoparticles and method of conjugation. The BSA-FIONs seem to show improved biocompatibility, as the haemolytic index is less than 2 % and cell viability is up to 120 %, when normalized with the control. The SAR value of BSAFIONs is 2300 Wg^(-1) when compared to 1700 Wg^(-1) of FIONs without BSA conjugation. Thus, we report here that BSA conjugation over FIONs(with a high saturation magnetization of 87 emug^(-1)) provide a single combinatorial approach to improve the biocompatibility and enhance the SAR value for magnetic hyperthermia, thus addressing both the current challenges of the same.

Magnetic labeling of primary murine monocytes using very small superparamagnetic iron oxide nanoparticles

Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.

Superparamagnetic iron oxide nanoparticles: promote neuronal regenerative capacity?

Currently,we know that neuronal outgrowth during development and regeneration requires a complex interaction of intra-and extracellular molecules such as growth factors,neurotransmitters and extracellular matrix proteins（O’Donnell et al.,2009）.Furthermore,the discovery of a broad spectrum of growth-promoting cues has led to novel concepts for thera-peutic strategies.

Influence of magnetic iron oxide nanoparticles on red blood cells and Caco-2 cells

The interactions of two types of cells (red blood cells, Caco-2 cells) with magnetic iron oxide nanoparticles (non-grafted, citrate-grafted, dendrimer-grafted) of 11 nm in size have been investigated. We focused on two important physiological parameters of the cells, the intracellular pH and the intracellular Ca2+ content. The results show that the nanoparticles do not have a significant influence on the pH and Ca2+ content of Caco-2 cells. The Ca2+ content of red blood cells is also not affected but the intracellular pH is slightly reduced.

Synthesis of Amine Terminated Pegylated Iron Oxide Nanoparticles for Prospective Astrocytoma Resection Grade Improvement

Having a survival rate to 5 years of only 3%,Glioblastoma’s(GBM)main treatment is surgical excision.Iron oxide nanoparticles have been proved to be a magnetic resonance imaging contrast agent and,if synthesized and tuned correctly,could be used to improve complete GBM resection.In this work monodisperse iron oxide nanoparticles were synthesized using thermal decomposition method,then a ligand exchange reaction with 3-aminopropyl trimethoxysilane(APS)was performed,following Pegylation of the particles using dicarboxylic acid PEG(PEG-diacid)and finally aminating with 2,2’-(ethylenedioxy)bis(ethylamine),last two by amide reactions.STEM and DLS demonstrate monodispersity(log σ<0.2)and desired size range to penetrate the blood-brain barrier(BBB);FT-IR shows the reactions were executed correctly and finally stability in deionized water,0.07 M NaCl and PBS 1X,as a function of 0-30 days,was tested.Results revealed the importance that the oleic acid/iron oleate molar ratio and the growth stage time represents for determining iron oxide nanoparticles’ size;as well as APS concentration and nucleation time influence on silica coating when performing the ligand exchange reaction.The produced iron oxide nanoparticles exhibit stability and proper amine terminated groups which are needed to allow easy incorporation of Chlorotoxin,a 36-amino acid peptide that binds specifically to astrocytoma cells,and a fluorescent molecule,which enables real time visualization of the tumor during surgery.

Characterization and Evaluation of Antibacterial Activities of Chemically Synthesized Iron Oxide Nanoparticles

The iron oxide nanoparticles have been synthesized in co-precipitation method using aqueous solution of ferric and ferrous ions with sodium salt. The synthesis of iron-oxide nanoparticles were validated by UV-Visible spectroscopy which showed higher peak at 370 nm as valid standard reference. An average size of iron oxide nanoparticle found by Diffraction Light scattering (DLS) particle size analyser, ranges approximately between 10 nm to 120 nm with mean particle size of 66 nm. The X-ray power diffraction (XRD) analysis revealed the crystallographic structure of magnetic particles. Characterization of the mean particle size and morphology of iron oxide nanoparticles confirmed that the iron oxide nanoparticles are nearly spherical and crystalline in shape. Further the antibacterial effect of iron oxide nanoparticles was evaluated against ten pathogenic bacteria which showed that the nanoparticles have moderate antibacterial activity against both Gram positive and Gram negative pathogenic bacterial strains and retains potential application in pharmaceutical and biomedical industries.

Synthesis and Characterization of Iron Oxide Nanoparticles Supported on Ziconia and Its Application in the Gas-Phase Oxidation of Cyclohexanol to Cyclohexanone

Iron oxide nanoparticles supported on zirconia were prepared by precipitation-deposition method and characterized by XRD, SEM, FT-IR, TGA/DTA, surface area and particle size analysis. Catalytic activities of the catalysts were tested in the gas-phase conversion of cyclohexanol in a fixed-bed flow type, Pyrex glass reactor, at 433 - 463 K. Major detected products were cyclohexanone, cyclohexene and benzene, depending on the used catalyst. The rate of reaction was significantly raised by the introduction of molecular oxygen in the feed gas, thereby suggesting the oxidation of cyclohexanol to cyclohexanone. Furthermore, the catalytic activity of iron oxide nanoparticles supported on zirconia treated with hydrogen at 553 K for 2 hours, was more selective and better than the unreduced iron oxide nanoparticles supported on zirconia, in the gas-phase oxidation of cyclohexanol to cyclohexanone. Experimental results showed that there was no leaching of metal, and that the catalyst was thus truly heterogeneous.

Fluorescence detection of Europiumdoped very small superparamagnetic iron oxide nanoparticles in murine hippocampal slice cultures

In the late 1980s,superparamagnetic iron oxide nanoparticles（SPIO）moved into focus as contrast agents in magnetic resonance imaging（MRI）,due to their strong relaxivity and resulting higher resolution of images.At the time,no one anticipated their high potential in basic research or for medical diagnostic andtreatment. Since then, SPIO have been evaluated notonly as spe- cific markers for MRI, but also for cell labeling and tracking （Li et al., 2013）.

Efficiency and Effectiveness Method versus ε-NTU Method with Application in Finned Flat Tube Compact Heat Exchanger with Water-Ethylene Glycol as Nanofluid Base of Iron Oxide Nanoparticles

This work aims to establish comparisons between two models used for the performance of heat exchangers. The chosen system, in this case, consists of a heat exchanger used in automotive radiators flat finned tube type. Water and ethylene glycol compound as base fluid and volume fractions of iron oxide nanoparticles (Fe3O4) are used as a refrigerant. The quantities determined in this work are the nanofluid exit temperature, the air exit temperature, the absolute error between the models for heat transfer rate, and Effectiveness. The quantities that constitute parameters, independent variables, are the airflow, represented by the Reynolds number, and the iron oxide volume fraction. Ethylene Glycol 50% compound has slightly better thermal performance than pure water and reduces the reactive effect of water on the environment, increasing the average life of the equipment. The absolute relative error between the models is less than 20% and presents maximum values with the increase of the nanoparticle volume fraction and growth in the Reynolds number for the air.

Balanites aegyptiaca Oil Synthesized Iron Oxide Nanoparticles: Characterization and Antibacterial Activity

Antibacterial activity of iron oxide nanoparticles, an employing B. aegyptiaca oil (L.) Del., was used as natural stabilizer by modifying a co-precipitation method. In this work, we chose B. aegyptiaca oil as the new surfactant coating agent, and synthesized B. aegyptiaca oil coating with iron oxide nanoparticles which were characterized with a variety of methods, including Gas Chromatography (GC) to determine the fatty acids composition of the seeds oil, Fourier Transform-Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM) equipped with Energy Dispersive Spectroscopy (EDS), X-ray Powder Diffractometer (XRD) and Vibrating Sample Magnetometer (VSM). In antibacterial studies, disk diffusion susceptibility test was used to measure efficacy of iron oxide nanoparticles against Gram-positive bacteria Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis) and Gram-negative bacteria Escherichia coli (E. coli) in terms of zone inhibition. The B. aegyptiaca coated on the surface of iron oxide nanoparticles;its particle size was found to be nanoscale below 50 nm, and the magnetization (δs) was 16.975 emu g-1. Antibacterial activity was measured. Efficacy of iron oxide nanoparticles against bacterial strains was found in Escherichia coli (E. coli). All these findings suggest that the nanoparticles synthesized from B. aegyptiaca oil may be a promising reagent for a wide variety of applications in biological fields as well as in nanomedicine.

Magnetic iron oxide nanoparticles carrying PTEN gene to reverse cisplatin-resistance of A549/CDDP cell lines

To evaluate the feasibility of using magnetic iron oxide nanoparticle as wild PTEN gene carrier for transfection in vitro to reverse cisplatin-resistance of A549/CDDP cells, A549/CDDP cells were transfected with the wild PTEN gene expression plasmid (pGFP-PTEN) by magnetic iron nanoparticle and lipo2000. The transfection efficiency was detected by fluorescence microscope and flow cytometer. The expression levels of PTEN mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry analysis. The effect of PTEN transfection on cell cycle enhances the sensitivity of A549/CDDP to cisplatin and nanoparticle-mediated transfection has a higher efficiency than that of the liposome-mediated group. The apoptosis level was up-regulated in PTEN transfection group. The magnetic iron oxide nanoparticle could be used as one of the ideal gene carriers for PTEN gene delivery in vitro. PTEN can be an effective target for reversing cisplatin-resistance in lung cancer.