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.

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.

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.

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.

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.

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.

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.

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）.

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.

Doping engineering of iron oxide nanoparticles towards high performance and biocompatible T_(1)-weighted MRI contrast agents

Extremely small-sized iron oxide nanoparticles(IONPs) are of great interest in magnetic resonance imaging(MRI) due to their biosafety as an alternative to clinical gadolinium(Ⅲ) complexes-based contrast agents.Especially when the particle size is less than 10 nm,it has strong diffusion ability and deep penetration distance in tumor tissue.Substitution doping can significantly enhance the T_(1)contrast effect of nanoparticles by regulating the surface exposed atoms.However,the nucleation and growth processes of multi-component synthesis systems are complex and difficult to be accurately controlled,leading to great challenges in the synthesis of ultra-small-sized nanoparticles with different components and sizes.Here,extremely smallsized superparamagnetic gadolinium-doped iron oxide nanoparticles(GdIONPs,Gd_(x)Fe_(3-x)O_(4) NPs) with adjustable doping amount and controllable size in the range of 3.5-7.5 nm were synthesized by thermal decomposition.Then,as-synthesized GdIONPs were surface modified with a highly water-soluble and biocompatible carboxyl-polyethylene glycol-phosphoric acid ligand with high binding affinity.Gd_(0.65)Fe_(2.35)O_(4) NPs exhibited very high r_(1) relaxivity of 10.6 mmol^(-1)·L·s^(-1) in terms of all metal concentrations and 49.0 mmol^(-1)·L·s^(-1) in terms of gadolinium alone,respectively,3 and 14 times higher than clinical T_(1) contrast agents(Gd-DTPA).GdIONPs can continuously obtain high resolution images of blood vessels,and can be used as an efficient and multifunctional contrast agent for MR T_(1)imaging.This stable and efficient doping strategy provides an easy and effective method to individually optimize the magnetic properties of complex oxides and their relaxation effects for a variety of biomedical applications.

Structural, Magnetic and Heating Efficiency of Ball Milled γ-Fe2O3/Gd2O3 Nanocomposite for Magnetic Hyperthermia

The preparation of γ-Fe2O3/Gd2O3 nanocomposite for possible use in magnetic hyperthermia application was done by ball milling technique. The nanocomposite was characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The heating efficiency and the effect of milling time (5 h and 30 h) on the structural and magnetic properties of the nanocomposite were reported. XRD analysis confirms the formation of the nanocomposite, while magnetization measurements show that the milled sample present hysteresis with low coercivity and remanence. The specific absorption rate (SAR) under an alternating magnetic field is investigated as a function of the milling time. A mean heating efficiency of 68 W/g and 28.7 W/g are obtained for 5 h and 30 h milling times respectively at 332 kHz and 170 Oe. The results showed that the obtained nanocomposite for 5 h milling time is a promising candidate for magnetic hyperthermia due to his properties which show an interesting magnetic behavior and high specific absorption rate.

Iron oxide nanoparticles:A promising approach for diagnosis and treatment of cardiovascular diseases

Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases(CVDs),it remains a leading cause of mortality and morbidity worldwide.This underscores the urgency for innovative approaches aiming at early and precise detection and treatment of CVDs to reduce the disease burden.Iron oxide nanoparticles(IONPs),with their unique magnetism and bioproperties,have shown great potential in this regard.In this review,we will begin with a brief overview of the synthesis and properties of IONPs.We will then focus on the latest applications of IONPs in CVDs,including diagnosis and treatment.The use of IONPs in the integration of diagnosis and treatment for CVDs is a promising field,and will be addressed in a separate section.The translational potential and challenges of IONPs will also be discussed.In conclusion,ongoing research and development of IONP-based strategies are highly likely to address current challenges effectively,and offer more personalized and efficient options for the diagnosis and treatment of CVDs.

Spy chemistry enables stable protein immobilization on iron oxide nanoparticles with enhanced magnetic properties

Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.

Magnetic nanoparticles conjugated with “RPE cell-MCP-1 antibody-VEGF antibody” compounds for the targeted therapy of age-related macular degeneration: a hypothesis

Age-related macular degeneration（AMD） is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium（RPE） transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1（MCP-1） expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor（VEGF） is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization（CNV）. We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles（SPIONs）. Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging（MRI）. This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.

Synthesis and characterization of Fe_3O_4@SiO_2 magnetic composite nanoparticles by a one-pot process

Fe3O4@SiO2 core–shell composite nanoparticles were successfully prepared by a one-pot process. Tetraethyl-orthosilicate was used as a surfactant to synthesize Fe3O4@SiO2 core–shell structures from prepared Fe3O4 nanoparticles. The properties of the Fe3O4 and Fe3O4@SiO2 composite nanoparticles were studied by X-ray diffraction, transmission electron microscopy, energy dispersive spectroscopy, and Fourier transform infrared spectroscopy. The prepared Fe3O4 particles were approximately 12 nm in size, and the thickness of the SiO2 coating was approximately 4 nm. The magnetic properties were studied by vibrating sample magnetometry. The results show that the maximum saturation magnetization of the Fe3O4@SiO2 powder（34.85 A·m^2·kg^–1） was markedly lower than that of the Fe3O4 powder（79.55 A·m^2·kg^–1）, which demonstrates that Fe3O4 was successfully wrapped by SiO2. The Fe3O4@SiO2 composite nanoparticles have broad prospects in biomedical applications; thus, our next study will apply them in magnetic resonance imaging.

Formation of multifunctional Fe_3O_4/Au composite nanoparticles for dual-mode MR/CT imaging applications

Recent advances with iron oxide/gold （Fe3O4/Au） composite nanoparticles （CNPs） in dual-modality magnetic reso- nance （MR） and computed tomography （CT） imaging applications are reviewed. The synthesis and assembly of＂dumbbell- like＂ and ＂core/shell＂ FeaO4/Au CNPs is introduced. Potential applications of some developed Fe3O4/Au CNPs as contrast agents for dual-mode MR/CT imaging applications are described in detail.

Synthesis and application of bilayer-surfactant-enveloped Fe_3O_4 nanoparticles: water-based bilayer-surfactant-enveloped ferrofluids

Superparamagnetic carbon-coated Fe3O4 nanoparticles with high magnetization（85 emu·g-（-1）） and high crystallinity were synthesized using polyethylene glycol-4000（PEG（4000）） as a carbon source.Fe3O4 water-based bilayer-surfactant-enveloped ferrofluids were subsequently prepared using sodium oleate and PEG（4000） as dispersants.Analyses using X-ray photoelectron spectroscopy,X-ray diffraction,and Fourier-transform infrared spectroscopy indicate that the Fe3O4 nanoparticles with a bilayer surfactant coating retain the inverse spinel-type structure and are successfully coated with sodium oleate and PEG（4000）.Transmission electron microscopy,vibrating sample magnetometry,and particle-size analysis results indicate that the coated Fe3O4 nanoparticles also retain the good saturation magnetization of Fe3O4（79.6 emu·g^-1） and that the particle size of the bilayer-surfactant-enveloped Fe3O4 nanoparticles is 42.97 nm,which is substantially smaller than that of the unmodified Fe3O4 nanoparticles（486.2 nm）.UV-vis and zeta-potential analyses reveal that the ferrofluids does not agglomerate for 120 h at a concentration of 4 g·L^-1,which indicates that the ferrofluids are highly stable.

Magnetic iron oxide nanoparticles accelerate osteogenic differentiation of mesenchymal stem cells via modulation of long noncoding RNA INZEB2

Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles （IONPs） have tissue-repairing effects. In the present study, we explored cellular effects of IONPs in mesenchymal stem cells （MSCs） and identified the underlying molecular mechanisms. The results showed that our as-prepared IONPs were structurally stable in MSCs and promoted osteogenic differentiation of MSCs as whole particles. Moreover, at the molecular level, we compared the gene expression of MSCs with or without IONP exposure and showed that IONPs upregulated long noncoding RNA INZEB2, which is indispensable for maintaining osteogenesis by MSCs. Furthermore, overexpression of INZEB2 downregulated ZEB2, a factor necessary to repress BMP/Smad- dependent osteogenic transcription. We also demonstrated that the essential role of INZEB2 in osteogenic differentiation was ZEB2-dependent. In summary, we elucidated the molecular basis of IONPs＇ effects on MSCs; these findings may serve as a meaningful theoretical foundation for applications of stem cells to regenerative medicine.