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Definition: Magnetic nanoparticles (MNPs) have great potential in various areas such as medicine, cancer therapy and diagnostics, biosensing, and material science. In particular, magnetite (Fe3O4) nanoparticles are extensively used for numerous bioapplications due to their biocompatibility, high saturation magnetization, chemical stability, large surface area, and easy functionalization. This paper describes magnetic nanoparticle physical and biological properties, emphasizing synthesis approaches, toxicity, and various biomedical applications, focusing on the most recent advancements in the areas of therapy, diagnostics, theranostics, magnetic separation, and biosensing. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic particle imaging (MPI) is a new imaging technology that directly detects superparamagnetic iron oxide nanoparticles. The technique has potential medical applications in angiography, cell tracking, and cancer detection. In this paper, the authors explore how nanoparticle relaxation affects image resolution. Historically, researchers have analyzed nanoparticle behavior by studying the time constant of the nanoparticle physical rotation. In contrast, in this paper, the authors focus instead on how the time constant of nanoparticle rotation affects the final image resolution, and this reveals nonobvious conclusions for tailoring MPI imaging parameters for optimal spatial resolution. Methods: The authors first extend x-space systems theory to include nanoparticle relaxation. The authors then measure the spatial resolution and relative signal levels in an MPI relaxometer and a 3D MPI imager at multiple drive field amplitudes and frequencies. Finally, these image measurements are used to estimate relaxation times and nanoparticle phase lags. Results: The authors demonstrate that spatial resolution, as measured by full-width at half-maximum, improves at lower drive field amplitudes. The authors further determine that relaxation in MPI can be approximated as a frequency-independent phase lag. These results enable the authors to accurately predict MPI resolution and sensitivity across a wide range of drive field amplitudes and frequencies. Conclusions: To balance resolution, signal-to-noise ratio, specific absorption rate, and magnetostimulation requirements, the drive field can be a low amplitude and high frequency. Continued research into how the MPI drive field affects relaxation and its adverse effects will be crucial for developing new nanoparticles tailored to the unique physics of MPI. Moreover, this theory informs researchers how to design scanning sequences to minimize relaxation-induced blurring for better spatial resolution or to exploit relaxation-induced blurring for MPI with molecular contrast. [ABSTRACT FROM AUTHOR]

Different chemical agents are used for the biocompatibility and/or functionality of the nanoparticles used in magnetic hyperthermia to reduce or even eliminate cellular toxicity and to limit the interaction between them (van der Waals and magnetic dipolar interactions), with highly beneficial effects on the efficiency of magnetic hyperthermia in cancer therapy. In this paper we propose an innovative strategy for the biocompatibility of these nanoparticles using gamma-cyclodextrins (γ-CDs) to decorate the surface of magnetite (Fe3O4) nanoparticles. The influence of the biocompatible organic layer of cyclodextrins, from the surface of Fe3O4 ferrimagnetic nanoparticles, on the maximum specific loss power in superparamagnetic hyperthermia, is presented and analyzed in detail in this paper. Furthermore, our study shows the optimum conditions in which the magnetic nanoparticles covered with gamma-cyclodextrin (Fe3O4–γ-CDs) can be utilized in superparamagnetic hyperthermia for an alternative cancer therapy with higher efficiency in destroying tumoral cells and eliminating cellular toxicity. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to detect and separate the cluster intensity provided by Iron oxide nanoparticles (IO-NPs), in the MRI images, to investigate the drug delivery effectiveness. IO-NPs were attached to the macrophages and inserted into the eye of the inflamed mouse's calf. The low resolution of MRI and the tiny dimension of the IO-NPs made the situation challenging. IO-NPs serve as a marker, due to their strong intensity in the MRI, enabling us to follow the track of the macrophages. An image processing procedure was developed to estimate the position and the amount of IO-NPs spreading inside the inflamed mouse leg. A fuzzy Clustering algorithm was adopted to select the region of interest (ROI). A 3D model of the femoral region was used for the detection and then the extraction IO-NPs in the MRI images. The results achieved prove the effectiveness of the proposed method to improve the control process of targeted drug delivered. It helps in optimizing the treatment and opens a promising novel research axis for nanomedicine applications. [ABSTRACT FROM AUTHOR]

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents. [ABSTRACT FROM AUTHOR]

35631580 3 Iacovita C., Fizesan I., Nitica S., Florea A., Barbu-Tudoran L., Dudric R., Pop A., Vedeanu N., Crisan O., Tetean R. Silica Coating of Ferromagnetic Iron Oxide Magnetic Nanoparticles Significantly Enhances Their Hyperthermia Performances for Efficiently Inducing Cancer Cells Death In Vitro. These researchers prepared bimetallic polyacrylic acid-coated Fe-Au core-satellite nanosystems to combine the magnetic and plasmonic properties of iron and gold nanoparticles in one core-shell. Finally, to selectively recognize the glycosylation profile of breast cancer cells, the nanoparticles were functionalized with lectin concanavalin A. Under external light irradiation, the resulting hybrid nanoparticles fully inhibited allograft solid tumor growth in murine models, thus demonstrating a great potential for combined magnetically assisted targeted delivery to tumor sites, tumor bioimaging, and treatment. The most stable formulation of coated nanoparticles presented an enhanced magnetic hyperthermia performance in water, and their specific absorption rate values increased by almost 1000 W/g SB Fe sb compared to bare Fe SB 3 sb O SB 4 sb nanoparticles. [Extracted from the article]

Here, selective anti-cancer activity of poly-l-lysine-functionalized iron oxide nanoparticles (PLL@IONPs) has been shown against osteosarcoma cancer. The mentioned nanoparticles were synthesized from Spinacia oleracia (spinach) leaf extract. In-vitro, osteosarcoma cells incubated with the synthesized nanoparticles showed the selective cytotoxicity. Particles exposed to the normal fibroblast cells displayed significantly less cytotoxic effects. Interestingly, the reactive oxygen species (ROS) generation was inhibited by the synthesized material with their intrinsic free radical scavenging activity. In-vivo, PLL@IONPs significantly inhibited the site-specific angiogenesis in chick embryo. This could lead to the site-specific therapeutic efficiency. In addition, suspected carcinogenic dyes were degraded by the particles and provided a cancer-preventive aspect. The results suggest that PLL@IONPs could be significantly applied as a therapeutic against osteosarcoma cancer as well as carcinogen degradation measure. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs)‐based tumor vaccines have the advantages of high safety and rapid activation of T cells, and have been approved for clinical tumor treatment. However, the conventional DC vaccines have some severe problems, such as poor activation of DCs in vitro, low level of antigen presentation, reduced cell viability, and difficulty in targeting lymph nodes in vivo, resulting in poor clinical therapeutic effects. In this research, magnetic nanoparticles Fe3O4@Ca/MnCO3 were prepared and used to actively and efficiently deliver antigens to the cytoplasm of DCs, promote antigen cross‐presentation and DC activation, and finally enhance the cellular immune response of DC vaccines. The results show that the magnetic nanoparticles can actively and quickly deliver antigens to the cytoplasm of DCs by regulating the magnetic field, and achieve cross‐presentation of antigens. At the same time, the nanoparticles degradation product Mn2+ enhanced immune stimulation through the interferon gene stimulating protein (STING) pathway, and another degradation product Ca2+ ultimately promoted cellular immune response by increasing autophagy. The DC vaccine constructed with the magnetic nanoparticles can more effectively migrate to the lymph nodes, promote the proliferation of CD8+ T cells, prolong the time of immune memory, and produce higher antibody levels. Compared with traditional DC vaccines, cytoplasmic antigen delivery with the magnetic nanoparticles provides a new idea for the construction of novel DC vaccines. [ABSTRACT FROM AUTHOR]

Cancer is one of the major health issues with increasing incidence worldwide. In spite of the existing conventional cancer treatment techniques, the cases of cancer diagnosis and death rates are rising year by year. Thus, new approaches are required to advance the traditional ways of cancer therapy. Currently, nanomedicine, employing nanoparticles and nanocomposites, offers great promise and new opportunities to increase the efficacy of cancer treatment in combination with thermal therapy. Nanomaterials can generate and specifically enhance the heating capacity at the tumor region due to optical and magnetic properties. The mentioned unique properties of nanomaterials allow inducing the heat and destroying the cancerous cells. This paper provides an overview of the utilization of nanoparticles and nanomaterials such as magnetic iron oxide nanoparticles, nanorods, nanoshells, nanocomposites, carbon nanotubes, and other nanoparticles in the thermal ablation of tumors, demonstrating their advantages over the conventional heating methods. [ABSTRACT FROM AUTHOR]

Magnetic Fe3O4 nanoparticles (MNPs) have great potential for nucleic acid separation, detection, and delivery. MNPs are considered a valuable tool in biomedicine due to their cost-effectiveness, stability, easy surface functionalization, and the possibility of the manipulations under a magnetic field. Herein, the synthesis of magnetic nylon 6 nanocomposites (MNPs@Ny6) was investigated. Transmission electron microscopy (TEM) was used for morphology and size analysis. A new method of UV-induced immobilization of oligonucleotides on MNPs@Ny6 for nucleic acid magnetic separation was proposed. MNPs@Ny6 shows a high oligonucleotide binding capacity of 2.2 nmol/mg with 73.3% loading efficiency. The proposed system has been applied to analyze model mixtures of target RNA on the total yeast RNA background. The RNA target isolation efficiency was 60% with high specificity. The bind RNA release was 88.8% in a quantity of 0.16 nmol/mg. The total RNA capture efficiency was 53%. Considering this, the MNPs@Ny6 is an attractive candidate for nucleic acids-specific magnetic isolation. [ABSTRACT FROM AUTHOR]

This review tries to summarize the purpose of steadily developing surface-functionalized nanoparticles for various bio-applications and represents a fascinating and rapidly growing field of research. Due to their unique properties—such as novel optical, biodegradable, low-toxicity, biocompatibility, size, and highly catalytic features—these materials are considered superior, and it is thus vital to study these systems in a realistic and meaningful way. However, rapid aggregation, oxidation, and other problems are encountered with functionalized nanoparticles, inhibiting their subsequent utilization. Adequate surface modification of nanoparticles with organic and inorganic compounds results in improved physicochemical properties which can overcome these barriers. This review investigates and discusses the iron oxide nanoparticles, gold nanoparticles, platinum nanoparticles, silver nanoparticles, and silica-coated nanoparticles and how their unique properties after fabrication allow for their potential use in a wide range of bio-applications such as nano-based imaging, gene delivery, drug loading, and immunoassays. The different groups of nanoparticles and the advantages of surface functionalization and their applications are highlighted here. In recent years, surface-functionalized nanoparticles have become important materials for a broad range of bio-applications. [ABSTRACT FROM AUTHOR]

Low-toxic colloidal superparamagnetic iron oxide nanoparticles (SPIONs) for theranostic applications were obtained by microwave-assisted technique. Nanoparticles were synthesized by the hydrothermal method under different conditions. XANES, XRD, and XPS studies support the maghemite (γ-Fe2O3) atomic and electronic structure of the nanoparticles. XANES data analysis reveals that nanoparticles have the structure reminiscent of the macroscopic maghemite. Mossbauer spectroscopy supports the γ-Fe2O3 phase of the nanoparticles and vibration magnetometry study shows that the nanoparticles appear to be superparamagnetic. Nanoparticle shape and size were studied by TEM and DLS methods. It was shown that the nanoparticles do not exceed 20 nm. Also, the nanoparticles are found to be low-toxic and did not have significant effects on the viability of the HeLa cell culture. The obtained nanoparticles generated heat with the highest ILP value of 2.56 nHm2/kg and can be considered potential candidates as heat mediators for local magnetic hyperthermia in oncology. [ABSTRACT FROM AUTHOR]

Abstract: We have performed a series of in vitro tests proposed for the reliable assessment of safety associated with nanoparticles-cell interaction. A thorough analysis of toxicity of three different coating iron oxide nanoparticles on HeLa cells has been carried out including, methyl thiazol tetrazolium bromide (MTT) and Trypan blue exclusion tests, cell morphology observation by optical and Scanning Electron Microscopy (SEM), study of cytoskeletal components, analysis of cell cycle and the presence of reactive oxygen species (ROS). We have quantified magnetic nanoparticle internalization, determined possible indirect cell damages and related it to the nanoparticle coating. The results confirm a very low toxicity of the analyzed iron oxide nanoparticles into HeLa cells by multiple assays and pave the way for a more successful cancer diagnostic and treatment without secondary effects. From the Clinical Editor: In this paper, three different iron oxide nanoparticles are studied and compared from the standpoint of safety and toxicity in HeLa cells, demonstrating low toxicity for each preparation, and paving the way to potential future clinical applications. [Copyright &y& Elsevier]

Peculiar features of the modification of Fe3O4 magnetic nanoparticles (MNPs) obtained by co-precipitation from solutions of FeII and FeIII salts (10-nm MNPs) and by the gas-condensation method (30-nm MNPs) with 3-aminopropylsilane and then with l-lysine were studied. The chemically obtained MNPs possess more pronounced hydrophilic properties and therefore readily form stable aqueous colloidal solutions and can be loaded with a larger amount of l-Lys. However, samples based on the physically obtained MNPs were characterized by more efficient internalization and longer retention times by the NIH 3T3 cells. The results obtained can be used in the design of novel nanomaterials for magnetic cell labeling. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticle's different applications in nanomedicine, due to their unique physical properties and biocompatibility, were intensively investigated. Recently, Fe3O4 nanoparticles, are confirmed to be the best sonosensitizers to enhance the performance of HIFU (high intensity focused ultrasound). They are also used as thermo-sensitizers in magnetic hyperthermia. A new idea of dual, magneto-ultrasound, coupled hyperthermia allows the ultrasound intensity to be reduced from the high to a moderate level. Our goal is to evaluate the enhancement of thermal effects of focused ultrasound of moderate intensity due to the presence of nanoparticles. We combine experimental results with numerical analysis. Experiments are performed on tissue-mimicking materials made of the 5% agar gel and gel samples containing Fe3O4 nanoparticles with φ = 100 nm with two fractions of 0.76 and 1.53% w/w. Thermocouples registered curves of temperature rising during heating by focused ultrasound transducer with acoustic powers of the range from 1 to 4 W. The theoretical model of ultrasound-thermal coupling is solved in COMSOL Multiphysics. We compared the changes between the specific absorption rates (SAR) coefficients determined from the experimental and numerical temperature rise curves depending on the nanoparticle fractions and applied acoustic powers. We confirmed that the significant role of nanoparticles in enhancing the thermal effect is qualitatively similarly estimated, based on experimental and numerical results. So that we demonstrated the usefulness of the FEM linear acoustic model in the planning of efficiency of nanoparticle-mediated moderate hyperthermia. [ABSTRACT FROM AUTHOR]

The ever-increasing biomedical application of magnetic nanoparticles (MNPs) implies increasing demand in their scalable and high-throughput production, with finely tuned and well-controlled characteristics. One of the options to meet the demand is microbial production by nanoparticles-synthesizing bacteria. This approach has several benefits over the standard chemical synthesis methods, including improved homogeneity of synthesis, cost-effectiveness, safety and eco-friendliness. There are, however, specific challenges emanating from the nature of the approach that are to be accounted and resolved in each manufacturing instance. Most of the challenges can be resolved by proper selection of the producing organism and optimizing cell culture and nanoparticles extraction conditions. Other issues require development of proper continuous production equipment, medium usage optimization and precursor ions recycling. This mini-review focuses on the related topics in microbial synthesis of MNPs: producing organisms, culturing methods, nanoparticles characteristics tuning, nanoparticles yield and synthesis timeframe considerations, nanoparticles isolation as well as on the respective challenges and possible solutions. [ABSTRACT FROM AUTHOR]

In recent decades, magnetic hyperthermia using magnetic nanoparticles, a promising but quite challenging method, has proven to be an effective cancer therapy procedure. In hyperthermia, heat, which is generated by magnetic nanoparticles exposed to a radiofrequency magnetic field, is employed to battle cancerous cells. Ideally, devices for magnetic hyperthermia should provide a variety of field amplitudes and frequencies for generating an appropriate and powerful alternating magnetic field. Here, we report the design and evaluation of a versatile system which provides different experimental setup possibilities for magnetic hyperthermia. The proposed system is a derivative of the Mazzilli inverter, which directly follows the resonant frequency of the LC tank circuit independent of its component. The feasibility of the system for hyperthermia studies was examined using iron oxide nanoparticles prepared by the coprecipitation method. Different experimental conditions including nanoparticles in solution and dispersed in gelatin phantoms were evaluated. Four different coils including two solenoids, a pancake, and a Helmholtz-like format were successfully tested. Using these coils, 18 different operation frequencies in the frequency band of 63–530 kHz with field strengths up to 27.2 kA/m were achieved. [ABSTRACT FROM AUTHOR]

Realizing the full potential of magnetic nanoparticles (MNPs) in nanomedicine requires the optimization of their physical and chemical properties. Elucidation of the effects of these properties on clinical diagnostic or therapeutic properties, however, requires the synthesis or purification of homogenous samples, which has proved to be difficult. While initial simulations indicated that size-selective separation could be achieved by flowing magnetic nanoparticles through a magnetic field, subsequent in vitro experiments were unable to reproduce the predicted results. Magnetic field-flow fractionation, however, was found to be an effective method for the separation of polydisperse suspensions of iron oxide nanoparticles with diameters greater than 20 nm. While similar methods have been used to separate magnetic nanoparticles before, no previous work has been done with magnetic nanoparticles between 20 and 200 nm. Both transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used to confirm the size of the MNPs. Further development of this work could lead to MNPs with the narrow size distributions necessary for their in vitro and in vivo optimization. [ABSTRACT FROM AUTHOR]

In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)–photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF–NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH–PT dual magneto-photothermal cancer therapy. [ABSTRACT FROM AUTHOR]