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Recently, iron oxide nanoparticles (NPs) have attracted much consideration due to their unique properties, such as superparamagnetism, surface-to-volume ratio, greater surface area, and easy separation methodology. Various physical, chemical, and biological methods have been adopted to synthesize magnetic NPs with suitable surface chemistry. This review summarizes the methods for the preparation of iron oxide NPs, size and morphology control, and magnetic properties with recent bioengineering, commercial, and industrial applications. Iron oxides exhibit great potential in the fields of life sciences such as biomedicine, agriculture, and environment. Nontoxic conduct and biocompatible applications of magnetic NPs can be enriched further by special surface coating with organic or inorganic molecules, including surfactants, drugs, proteins, starches, enzymes, antibodies, nucleotides, nonionic detergents, and polyelectrolytes. Magnetic NPs can also be directed to an organ, tissue, or tumor using an external magnetic field for hyperthermic treatment of patients. Keeping in mind the current interest in iron NPs, this review is designed to report recent information from synthesis to characterization, and applications of iron NPs.

A broad spectrum of nanomaterials has been investigated for multiple purposes in recent years. Some of these studied materials are magnetics nanoparticles (MNPs). Iron oxide nanoparticles (IONPs) and superparamagnetic iron oxide nanoparticles (SPIONs) are MNPs that have received extensive attention because of their physicochemical and magnetic properties and their ease of combination with organic or inorganic compounds. Furthermore, the arresting of these MNPs into a cross-linked matrix known as hydrogel has attracted significant interest in the biomedical field. Commonly, MNPs act as a reinforcing material for the polymer matrix. In the present review, several methods, such as co-precipitation, polyol, hydrothermal, microemulsion, and sol-gel methods, are reported to synthesize magnetite nanoparticles with controllable physical and chemical properties that suit the required application. Due to the potential of magnetite-based nanocomposites, specifically in hydrogels, processing methods, including physical blending, in situ precipitation, and grafting methods, are introduced. Moreover, the most common characterization techniques employed to study MNPs and magnetic gel are discussed.

Magnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T₁-weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents. We show that SNIOs permeate biological tissue effectively following injection into brain parenchyma or cerebrospinal fluid. We also demonstrate that SNIOs readily enter the brain following ultrasound-induced blood–brain barrier disruption, emulating the performance of a gadolinium agent and providing a basis for future biomedical applications. These results thus demonstrate a platform for MRI probe development that combines advantages of smallmolecule imaging agents with the potency of nanoscale materials.

Clove and green Coffee (g-Coffee) extracts were used to synthesize green iron oxide nanoparticles, which were then used to sorb Cd 2+ and Ni 2+ ions out of an aqueous solution. Investigations with x-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, nitrogen adsorption and desorption (BET), Zeta potential, and scanning electron microscopy were performed to know and understand more about the chemical structure and surface morphology of the produced iron oxide nanoparticles. The characterization revealed that the main component of iron nanoparticles was magnetite when the Clove extract was used as a reducing agent for Fe 3+ , but both magnetite and hematite were included when the g-Coffee extract was used. Sorption capacity for metal ions was studied as a function of sorbent dosage, metal ion concentration, and sorption period. The maximum Cd 2+ adsorption capacity was 78 and 74 mg/g, while that of Ni 2+ was 64.8 and 80 mg/g for iron nanoparticles prepared using Clove and g-Coffee, respectively. Different isotherm and kinetic adsorption models were used to fit experimental adsorption data. Adsorption of Cd 2+ and Ni 2+ on the iron oxide surface was found to be heterogeneous, and the mechanism of chemisorption is involved in the stage of determining the rate. The correlation coefficient R 2 and error functions like RMSE, MES and MAE were used to evaluate the best fit models to the experimental adsorption data. The adsorption mechanism was explored using FTIR analysis. Antimicrobial study showed broad spectrum antibacterial activity of the tested nanomaterials against both Gram positive ( S. aureus ) (25923) and Gram negative ( E. coli ) (25913) bacteria with increased activity against Gram positive bacteria than Gram negative one and more activity for Green iron oxide nanoparticles prepared from Clove than g-Coffee one.

The recent, fast development of nanotechnology is reflected in the medical sciences. Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are an excellent example. Thanks to their superparamagnetic properties, SPIONs have found application in Magnetic Resonance Imaging (MRI) and magnetic hyperthermia. Unlike bulk iron, SPIONs do not have remnant magnetization in the absence of the external magnetic field; therefore, a precise remote control over their action is possible. This makes them also useful as a component of the advanced drug delivery systems. Due to their easy synthesis, biocompatibility, multifunctionality, and possibility of further surface modification with various chemical agents, SPIONs could support many fields of medicine. SPIONs have also some disadvantages, such as their high uptake by macrophages. Nevertheless, based on the ongoing studies, they seem to be very promising in oncological therapy (especially in the brain, breast, prostate, and pancreatic tumors). The main goal of our paper is, therefore, to present the basic properties of SPIONs, to discuss their current role in medicine, and to review their applications in order to inspire future developments of new, improved SPION systems.

Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe O NPs) have shown great potential as an advanced platform because of their inherent magnetic resonance imaging (MRI), biocatalytic activity (nanozyme), magnetic hyperthermia treatment (MHT), photo-responsive therapy and drug delivery for chemotherapy and gene therapy. Magnetic Fe O NPs can be synthesized through several methods and easily surface modified with biocompatible materials or active targeting moieties. The MRI capacity could be appropriately modulated to induce response between and modes by controlling the size distribution of Fe O NPs. Besides, small-size nanoparticles are also desired due to the enhanced permeation and retention (EPR) effect, thus the imaging and therapeutic efficiency of Fe O NP-based platforms can be further improved. Here, we firstly retrospect the typical synthesis and surface modification methods of magnetic Fe O NPs. Then, the latest biomedical application including responsive MRI, multimodal imaging, nanozyme, MHT, photo-responsive therapy and drug delivery, the mechanism of corresponding treatments and cooperation therapeutics of multifunctional Fe O NPs are also be explained. Finally, we also outline a brief discussion and perspective on the possibility of further clinical translations of these multifunctional nanomaterials. This review would provide a comprehensive reference for readers to understand the multifunctional Fe O NPs in cancer diagnosis and treatment.

Background Iron oxide nanoparticles have been approved by food and drug administration for clinical application as magnetic resonance imaging (MRI) and are considered to be a biocompatible material. Large iron oxide nanoparticles are usually used as transversal ( T 2 ) contrast agents to exhibit dark contrast in MRI. In contrast, ultrasmall iron oxide nanoparticles (USPIONs) (several nanometers) showed remarkable advantage in longitudinal ( T 1 )-weighted MRI due to the brighten effect. The study of the toxicity mainly focuses on particles with size of tens to hundreds of nanometers, while little is known about the toxicity of USPIONs. Results We fabricated Fe 3 O 4 nanoparticles with diameters of 2.3, 4.2, and 9.3 nm and evaluated their toxicity in mice by intravenous injection. The results indicate that ultrasmall iron oxide nanoparticles with small size (2.3 and 4.2 nm) were highly toxic and were lethal at a dosage of 100 mg/kg. In contrast, no obvious toxicity was observed for iron oxide nanoparticles with size of 9.3 nm. The toxicity of small nanoparticles (2.3 and 4.2 nm) could be reduced when the total dose was split into 4 doses with each interval for 5 min. To study the toxicology, we synthesized different-sized SiO 2 and gold nanoparticles. No significant toxicity was observed for ultrasmall SiO 2 and gold nanoparticles in the mice. Hence, the toxicity of the ultrasmall Fe 3 O 4 nanoparticles should be attributed to both the iron element and size. In the in vitro experiments, all the ultrasmall nanoparticles (< 5 nm) of Fe 3 O 4 , SiO 2 , and gold induced the generation of the reactive oxygen species (ROS) efficiently, while no obvious ROS was observed in larger nanoparticles groups. However, the ·OH was only detected in Fe 3 O 4 group instead of SiO 2 and gold groups. After intravenous injection, significantly elevated ·OH level was observed in heart, serum, and multiple organs. Among these organs, heart showed highest ·OH level due to the high distribution of ultrasmall Fe 3 O 4 nanoparticles, leading to the acute cardiac failure and death. Conclusion Ultrasmall Fe 3 O 4 nanoparticles (2.3 and 4.2 nm) showed high toxicity in vivo due to the distinctive capability in inducing the generation of ·OH in multiple organs, especially in heart. The toxicity was related to both the iron element and size. These findings provide novel insight into the toxicology of ultrasmall Fe 3 O 4 nanoparticles, and also highlight the need of comprehensive evaluation for their clinic application. Graphical Abstract

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T₁ contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.

Iron oxides are chemical compounds which have different polymorphic forms, including γ-Fe2O3 (maghemite), Fe3O4 (magnetite), and FeO (wustite). Among them, the most studied are γ-Fe2O3 and Fe3O4, as they possess extraordinary properties at the nanoscale (such as super paramagnetism, high specific surface area, biocompatible etc.), because at this size scale, the quantum effects affect matter behavior and optical, electrical and magnetic properties. Therefore, in the nanoscale, these materials become ideal for surface functionalization and modification in various applications such as separation techniques, magnetic sorting (cells and other biomolecules etc.), drug delivery, cancer hyperthermia, sensing etc., and also for increased surface area-to-volume ratio, which allows for excellent dispersibility in the solution form. The current methods used are partially and passively mixed reactants, and, thus, every reaction has a different proportion of all factors which causes further difficulties in reproducibility. Direct active and complete mixing and automated approaches could be solutions to this size- and shape-controlled synthesis, playing a key role in its exploitation for scientific or technological purposes. An ideal synthesis method should be able to allow reliable adjustment of parameters and control over the following: fluctuation in temperature; pH, stirring rate; particle distribution; size control; concentration; and control over nanoparticle shape and composition i.e., crystallinity, purity, and rapid screening. Iron oxide nanoparticle (IONP)-based available clinical applications are RNA/DNA extraction and detection of infectious bacteria and viruses. Such technologies are important at POC (point of care) diagnosis. IONPs can play a key role in these perspectives. Although there are various methods for synthesis of IONPs, one of the most crucial goals is to control size and properties with high reproducibility to accomplish successful applications. Using multiple characterization techniques to identify and confirm the oxide phase of iron can provide better characterization capability. It is very important to understand the in-depth IONP formation mechanism, enabling better control over parameters and overall reaction and, by extension, properties of IONPs. This work provides an in-depth overview of different properties, synthesis methods, and mechanisms of iron oxide nanoparticles (IONPs) formation, and the diverse range of their applications. Different characterization factors and strategies to confirm phase purity in the IONP synthesis field are reviewed. First, properties of IONPs and various synthesis routes with their merits and demerits are described. We also describe different synthesis strategies and formation mechanisms for IONPs such as for: wustite (FeO), hematite (α-Fe2O3), maghemite (ɤ-Fe2O3) and magnetite (Fe3O4). We also describe characterization of these nanoparticles and various applications in detail. In conclusion, we present a detailed overview on the properties, size-controlled synthesis, formation mechanisms and applications of IONPs.