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The contactless heating capacity of magnetic nanoparticles (MNPs) has been exploited in fields such as hyperthermia cancer therapy, catalysis, and enzymatic thermal regulation. Herein, we propose an advanced technology to generate multiple local temperatures in a single-pot reactor by exploiting the unique nanoheating features of iron oxide MNPs exposed to alternating magnetic fields (AMFs). The heating power of the MNPs depends on their magnetic features but also on the intensity and frequency conditions of the AMF. Using a mixture of diluted colloids of MNPs we were able to generate a multi-hot-spot reactor in which each population of MNPs can be selectively activated by adjusting the AMF conditions. The maximum temperature reached at the surface of each MNP was registered using independent fluorescent thermometers that mimic the molecular link between enzymes and MNPs. This technology paves the path for the implementation of a selective regulation of multienzymatic reactions.
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Hipertermia Induzida , Nanopartículas de Magnetita , Nanopartículas , Campos Magnéticos , Nanopartículas Magnéticas de Óxido de Ferro , MagnetismoRESUMO
In hepatocytes, PLIN2 is the major protein coating lipid droplets (LDs), an organelle the hepatitis C virus (HCV) hijacks for virion morphogenesis. We investigated the consequences of PLIN2 deficiency on LDs and on HCV infection. Knockdown of PLIN2 did not affect LD homeostasis, likely due to compensation by PLIN3, but severely impaired HCV particle production. PLIN2-knockdown cells had slightly larger LDs with altered protein composition, enhanced local lipase activity and higher ß-oxidation capacity. Electron micrographs showed that, after PLIN2 knockdown, LDs and HCV-induced vesicular structures were tightly surrounded by ER-derived double-membrane sacs. Strikingly, the LD access for HCV core and NS5A proteins was restricted in PLIN2-deficient cells, which correlated with reduced formation of intracellular HCV particles that were less infectious and of higher density, indicating defects in maturation. PLIN2 depletion also reduced protein levels and secretion of ApoE due to lysosomal degradation, but did not affect the density of ApoE-containing lipoproteins. However, ApoE overexpression in PLIN2-deficient cells did not restore HCV spreading. Thus, PLIN2 expression is required for trafficking of core and NS5A proteins to LDs, and for formation of functional low-density HCV particles prior to ApoE incorporation.This article has an associated First Person interview with the first author of the paper.
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Hepacivirus/patogenicidade , Hepatite C/virologia , Hepatócitos/virologia , Gotículas Lipídicas/virologia , Lipoproteínas/metabolismo , Perilipina-2/metabolismo , Vírion/fisiologia , Células HEK293 , Hepatite C/metabolismo , Hepatócitos/metabolismo , Humanos , Gotículas Lipídicas/metabolismo , Perilipina-2/genética , Proteínas não Estruturais Virais/metabolismo , Replicação ViralRESUMO
OBJECTIVE: Toxicity from off-target heating with magnetic hyperthermia (MHT) is generally assumed to be understood. MHT research focuses on development of more potent heating magnetic iron oxide nanoparticles (MIONs), yet our understanding of factors that define biodistribution following systemic delivery remains limited. Preclinical development relies on mouse models, thus understanding off-target heating with MHT in mice provides critical knowledge for clinical development. METHODS: Eight-week old female nude mice received a single tail vein injection of bionized nanoferrite (BNF) MIONs or a counterpart labeled with a polyclonal human antibody (BNF-IgG) at 1 mg, 3 mg or 5 mg Fe/mouse on day 1. On day 3, mice were exposed to an alternating magnetic field (AMF) having amplitude of 32, 48 or 64 kA/m at â¼145 kHz for 20 min. Twenty-four hours later, blood, livers and spleens were harvested and analyzed. RESULTS: Damage to livers was apparent by histology and serum liver enzymes following MHT with BNF or BNF-IgG at doses ≥3 mg Fe and AMF amplitudes ≥48 kA/m. Differences between effects with BNF vs. BNF-IgG at a dose of 3 mg Fe were noted in all measures, with less damage and increased survival occurring in mice injected with BNF-IgG. Necropsies revealed severe damage to duodenum and upper small intestines, likely the immediate cause of death at the highest MHT doses. CONCLUSION: Results demonstrate that the MION coating affects biodistribution, which in turn determines off-target effects. Developments to improve heating capabilities of MIONs may be clinically irrelevant without better control of biodistribution.
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Hipertermia Induzida , Nanopartículas , Animais , Feminino , Camundongos , Hipertermia Induzida/efeitos adversos , Campos Magnéticos , Nanopartículas Magnéticas de Óxido de Ferro , Camundongos Nus , Distribuição TecidualRESUMO
Most iron oxide nanoparticles applications, and in special biomedical applications, require the accurate determination of iron content as the determination of particle properties from measurements in dispersions is strongly dependent on it. Inductively coupled plasma (ICP) and spectrophotometry are two typical worldwide used analytical methods for iron concentration determination. In both techniques, precise determination of iron is not straightforward and nanoparticle digestion and dilution procedures are needed prior to analysis. The sample preparation protocol has been shown to be as important as the analytical method when accuracy is aimed as many puzzling reported results in magnetic, colloidal, and structural properties are simply attributable to inadequate dissolution procedures. Therefore, a standard sample preparation protocol is needed to ensure the adequate and complete iron oxide nanoparticle dissolution and to harmonize this procedure. In this work, an interlaboratory evaluation of an optimized iron oxide nanoparticle digestion/dilution protocol was carried out. The presented protocol is simple, inexpensive, and does not involve any special device (as microwave, ultrasound, or other high-priced digestion devices). Then, iron concentration was measured by ICP-OES (performed in ICMM/CSIC-Spain) and spectrophotometry (NanoPET-Germany) and the obtained concentration values were analyzed to determine the most probable error causes. Uncertainty values as low as 1.5% were achieved after the optimized method was applied. Moreover, this article provides a list of recommendations to significantly reduce uncertainty in both sample preparation and analysis procedures. Graphical abstract á .
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Iron oxide nanoparticles have been used in preclinical studies to label stem cells for non-invasive tracking and homing. The search continues for novel particle candidates that are suitable for clinical applications. Since standard analyses to investigate cell-particle interactions and safety are labor-intensive, an efficient procedure is required to guide future particle development and to exclude adverse health effects. The application of combined Raman trapping microscopy with fluidic chips is reported for the analysis of single cells labeled with different types of aminated iron oxide particles. Multivariate data analysis revealed Raman signal differences that could be clearly assigned to cell-particle interactions and cytotoxicity, respectively. A validation dataset verified that more than 95 % of the spectra were correctly classified. Thus, our approach enables rapid discrimination of non-hazardous from cytotoxic nanoparticles as a prerequisite for safe clinical applications.
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Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/química , Análise de Célula Única , Humanos , Células-Tronco Mesenquimais/citologia , Análise Espectral RamanRESUMO
Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-ß (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lacking iron, nor iron-containing dextran-coated parenteral iron replacement agent, induced significant antitumor effects, suggesting a dependence on the type of IONP formulation. Analysis of multiple independent clinical databases supports a hypothesis that upregulation of TLR3 and IRF3 correlates with increased overall survival among breast cancer patients. Taken together, these data support a compelling rationale to re-examine IONP formulations as harboring anticancer immune (nano)adjuvant properties to generate a therapeutic benefit without requiring uptake by cancer cells.
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Neoplasias da Mama , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Modelos Animais de Doenças , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Ferro , Amido , Nanopartículas Magnéticas de Óxido de FerroRESUMO
Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.
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Hipertermia Induzida , Nanopartículas de Magnetita , Termometria , Medicina de Precisão , Diagnóstico por Imagem/métodos , Nanopartículas de Magnetita/uso terapêutico , Campos MagnéticosRESUMO
Besides neutralizing antibodies, which are considered an important measure for vaccine immunogenicity, Fc-mediated antibody functions can contribute to antibody-mediated protection. They are strongly influenced by structural antibody properties such as subclass and Fc glycan composition. We here applied a systems serology approach to dissect humoral immune responses induced by MVA-MERS-S, an MVA-vectored vaccine against the Middle East respiratory syndrome coronavirus (MERS-CoV). Building on preceding studies reporting the safety and immunogenicity of MVA-MERS-S, our study highlights the potential of a late boost, administered one year after prime, to enhance both neutralizing and Fc-mediated antibody functionality compared to the primary vaccination series. Distinct characteristics were observed for antibodies specific to the MERS-CoV spike protein S1 and S2 subunits, regarding subclass and glycan compositions as well as Fc functionality. These findings highlight the benefit of a late homologous booster vaccination with MVA-MERS-S and may be of interest for the design of future coronavirus vaccines.
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A summary of recent developments in the synthesis, stabilisation and coating of magnetic iron oxide nanoparticles for hyperthermia applications is presented. Methods for synthesis in aqueous, organic and microemulsion systems are reviewed together with the resulting heating rates of the nanoparticles. Different stabilisation mechanisms for iron oxide nanoparticles from aqueous and organic media are discussed as intermediates for further coating and functionalisation. Coating with silica and/or polysaccharides is mainly used for design of nanoparticles especially for targeted hyperthermia application. These coatings permit versatile functionalisation as a basis for conjugating biomolecules, e.g. antibodies or peptides. Various strategies to conjugate biomolecules on the particle surface are discussed, with emphasis on methods that preserve biofunctionality after immobilisation. The efficiency of established methods such as carbodiimide coupling and oriented conjugation strategies is compared with new developments such as the bioorthogonal approaches that are based on the cycloaddition of strain-promoted alkynes with azides or nitrones. For targeted hyperthermia applications the study of the formation of a protein corona around nanoparticles with site-specific biomolecules on the surface is essential to achieve improved circulation times in the blood and reduced non-specific uptake by non-targeted organs for a high specific accumulation in the target tissue.
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Compostos Férricos/química , Nanopartículas Metálicas/química , Animais , Compostos Férricos/uso terapêutico , Humanos , Hipertermia Induzida , Nanopartículas Metálicas/uso terapêuticoRESUMO
Nanoparticle-based formulations are considered valuable tools for diagnostic and treatment purposes. The surface decoration of nanoparticles with polyethyleneimine (PEI) is often used to enhance their targeting and functional properties. Here, we aimed at addressing the long-term fate in vivo and the potential "off-target" effects of PEI decorated iron oxide nanoparticles (PEI-MNPs) in individuals with low-grade and persistent systemic inflammation. For this purpose, we synthesized PEI-MNPs (core-shell method, PEI coating under high pressure homogenization). Further on, we induced a low-grade and persistent inflammation in mice through regular subcutaneous injection of pathogen-associated molecular patterns (PAMPs, from zymosan). PEI-MNPs were injected intravenously. Up to 7 weeks thereafter, the blood parameters were determined via automated fluorescence flow cytometry, animals were euthanized, and the organs analyzed for iron contents (atomic absorption spectrometry) and for expression of NF-κB associated proteins (p65, IκBα, p105/50, p100/52, COX-2, Bcl-2, SDS-PAGE and Western blotting). We observed that the PEI-MNPs had a diameter of 136 nm and a zeta-potential 56.9 mV. After injection in mice, the blood parameters were modified and the iron levels were increased in different organs. Moreover, the liver of animals showed an increased protein expression of canonical NF-κB signaling pathway members early after PEI-MNP application, whereas at the later post-observation time, members of the non-canonical signaling pathway were prominent. We conclude that the synergistic effect between PEI-MNPs and the low-grade and persistent inflammatory state is mainly due to the hepatocytes sensing infection (PAMPs), to immune responses resulting from the intracellular metabolism of the uptaken PEI-MNPs, or to hepatocyte and immune cell communications. Therefore, we suggest a careful assessment of the safety and toxicity of PEI-MNP-based carriers for gene therapy, chemotherapy, and other medical applications not only in healthy individuals but also in those suffering from chronic inflammation.
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Gastrointestinal infections are a major cause for serious clinical complications in infants. The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++ CD4+ T cells (TFH cells). We investigated the ontogeny of CXCR5+PD-1++ CD4+ T cells in human intestines. While CXCR5+PD-1++ CD4+ T cells were absent in fetal intestines, CXCR5+PD-1++ CD4+ T cells increased after birth and were abundant in infant intestines, resulting in significant higher numbers compared to adults. These findings were supported by scRNAseq analyses, showing increased frequencies of CD4+ T cells with a TFH gene signature in infant intestines compared to blood. Co-cultures of autologous infant intestinal CXCR5+PD-1+/-CD4+ T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells. Taken together, we demonstrate that functional TFH cells are numerous in infant intestines, making them a promising target for oral pediatric vaccine strategies.
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Linfócitos T CD4-Positivos , Receptor de Morte Celular Programada 1 , Linfócitos T Auxiliares-Indutores , Adulto , Criança , Humanos , Lactente , Linfócitos B , Receptores CXCR5 , Linfócitos T CD4-Positivos/imunologiaRESUMO
We have developed a nano-rheological characterization tool to extract the frequency- and scale-dependent rheological properties of soft materials during oral processing. Taking advantage of AC susceptometry, the dynamic magnetization of magnetic nanoparticles blended in the matrix material is measured. The magnetic AC susceptibility spectra of the particles are affected by the viscosity and mechanical modulus of the matrix material and provide the rheological properties of the matrix. Commercially available iron-oxide magnetic nanoparticles with 80 and 100 nm particle sizes are used as tracers in the frequency range of 1 Hz-10 kHz. The AC susceptibility is measured using two differentially connected coils, and the effects of the sample temperature and distance with respect to the detection coils are investigated. The developed measurement setup shows the feasibility of remote nano-rheological measurements up to 2 cm from the coil system, which can be used to, e.g., monitor the texture of matrix materials during oral processing.
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Magnetic particle imaging (MPI) is a noninvasive tomographic imaging modality for the quantitative visualization of magnetic nanoparticles (MNPs) with high temporal and spatial resolution. The general capability of MPI for cell tracking (e.g., monitoring living cells labeled with MNPs) has successfully been shown. MNPs in cell culture media are often subjected to structural and magnetic changes. In addition to the deteriorating reproducibility, this also complicates the systematic study of the relationship between the MNP properties and their cellular uptake for MPI. Here, we present a method for the preparation of magnetically labeled THP-1 (Tamm-Horsfall Protein-1) monocytes that are used in MPI cell tracking. The method development was performed using two different MPI tracers, which exhibited electrostatic and steric stabilizations, respectively. In the first step, the interaction between the MNPs and cell culture media was investigated and adjusted to ensure high structural and magnetic stability. Furthermore, the influences of the incubation time, MNP concentration used for cellular uptake, and individual preparation steps (e.g., the washing of cells) were systematically investigated. Finally, the success of the developed loading method was demonstrated by the MPI measurements. The presented systematic investigation of the factors that influence the MNP loading of cells will help to develop a reliable and reproducible method for MPI monocyte tracking for the early detection of inflammation in the future.
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Rastreamento de Células , Nanopartículas de Magnetita , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Monócitos , Reprodutibilidade dos Testes , UromodulinaRESUMO
AIM: In this study, the influence of a serum albumin (SA) and human plasma (HP) derived protein- and lipid molecule corona on the toxicity and biodegradability of different iron oxide nanoparticles (IONP) was investigated. METHODS: IONP were synthesized and physicochemically characterized regarding size, charge, and colloidal stability. The adsorbed proteins were quantified and separated by gel electrophoresis. Adsorbed lipids were profiled by ultraperformance liquid chromatography-ESI-tandem mass spectrometry. The biocompatibility was investigated using isolated erythrocytes and a shell-less hen's egg model. The biodegradability was assessed by iron release studies in artificial body fluids. RESULTS: The adsorption patterns of proteins and lipids varied depending on the surface characteristics of the IONP like charge and hydrophobicity. The biomolecule corona modified IONP displayed favorable colloidal stability and toxicological profile compared to IONP without biomolecule coronas, reducing erythrocyte aggregation and hemolysis in vitro as well as the corresponding effects ex ovo/in vivo. The coronas decreased the degradation speed of all tested IONP compared to bare particles, but, whereas all IONP degraded at the same rate for the SA corona, substantial differences were evident for IONP with HP-derived corona depending on the lipid adsorption profile. CONCLUSION: In this study the impact of the proteins and lipids in the biomolecule corona on the entire IONP application cycle from the injection process to the degradation was demonstrated.
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Nanopartículas , Coroa de Proteína , Animais , Galinhas , Feminino , Humanos , Lipídeos , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas/toxicidadeRESUMO
Fully mature DC and, to a lesser extent, activated T and B cells express CD83, a surface molecule that appears to fulfil an important role in efficient T-cell activation. Recently, it has been shown that CD83 mRNA is transported from the nucleus to the cytoplasm by an uncommon route, involving the cellular RNA-binding protein HuR and the nuclear export receptor CRM1. Moreover, the shuttle phosphoprotein APRIL (ANP32B) has been shown to be required for HuR-mediated nucleocytoplasmic translocation of the CD83 mRNA by acting as an adaptor that links HuR and CRM1. Here, we are able to report that casein kinase 2 (CK2) phosphorylates APRIL on residue threonine244 (Thr(244)) and demonstrate that the CK2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes CD83 expression in activated Jurkat T cells by interfering with the nucleocytoplasmic translocation of CD83 mRNA. Depletion and knockdown studies demonstrate that the CK2 alpha' subunit is necessary for this regulation, whereas the CK2 alpha subunit seems to be dispensable. Taken together, the data presented significantly extend our knowledge of the complex regulation of CD83 mRNA processing and provides a novel strategy to interfere with CD83 expression.
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Antígenos CD/metabolismo , Antígenos de Superfície/metabolismo , Caseína Quinase II/metabolismo , Imunoglobulinas/metabolismo , Carioferinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Antígenos CD/efeitos dos fármacos , Caseína Quinase II/antagonistas & inibidores , Linhagem Celular Tumoral , Proteínas ELAV , Proteína Semelhante a ELAV 1 , Vetores Genéticos/metabolismo , Células HeLa , Humanos , Imunoglobulinas/efeitos dos fármacos , Células Jurkat , Glicoproteínas de Membrana/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Fosforilação/fisiologia , Transfecção , Triazóis/farmacologia , Proteína Exportina 1 , Antígeno CD83RESUMO
Fluorochrome-labelled iron oxide magnetic nanoparticles (MNP) have been of great help in elucidating biological processes. Here, we used dually-fluorochrome-labelled MNP and studied to what extent fluorescence detection could reflect their fate in living animals. One day after application in mice (200 µmol Fe/kg body weight), the fluorescence of the dye attached to the core (DY-730) was very prominent and in agreement with the increase of iron in the liver and spleen of mice, but inconspicuous at time points thereafter. We attribute this fluorescence behavior to early degradation processes of the MNP´s core in the cellular lysosomal compartment. In contrast, the fluorescence of the dye DY-555 stuck to the PEG coating was not detectable in vivo. In summary, labelling of MNP with dyes at their metallic core could be of help when detecting first incidences of MNP biodegradation in vivo, as opposed to dyes attached to the MNP coating.
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Technologically relevant magnetic nanoparticles for biomedicine are rarely noninteracting single-domain nanoparticles; instead, they are often interacting, with complex physical and magnetic structures. In this paper, we present both experimental and simulated magnetic hysteresis loops of a system of magnetic nanoparticles with significant interparticle interactions and a well-defined intraparticle structure which are used for magnetic nanoparticle hyperthermia cancer treatment. Experimental measurements were made at 11 K on suspensions of magnetic nanoparticles dispersed in H2O which have been frozen in a range of applied magnetic fields to tune the interparticle interactions. Micromagnetic simulations of hysteresis loops investigated the roles of particle orientation with respect to the field and of particle chaining in the shape of the hysteresis loops. In addition, we present an analysis of the magnetic anisotropy arising from the combination of magnetocrystalline and shape anisotropy, given the well-defined internal structure of the nanoparticles. We find that the shape of the experimental hysteresis loops can be explained by the internal magnetic structure, modified by the effects of interparticle interactions from chaining.
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Aim: To simulate the stability and degradation of superparamagnetic iron oxide nanoparticles (MNP) in vitro as part of their life cycle using complex simulated biological fluids. Materials & methods: A set of 13 MNP with different polymeric or inorganic shell materials was synthesized and characterized regarding stability and degradation of core and shell in simulated biological fluids. Results: All MNP formulations showed excellent stability during storage and in simulated body fluid. In endosomal/lysosomal media the degradation behavior depended on shell characteristics (e.g., charge, acid-base character) and temperature enabling the development of an accelerated stress test protocol. Conclusion: Kinetics of transformations depending on the MNP type could be established to define structure-activity relationships as prediction model for rational particle design.
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Compostos Férricos/química , Nanopartículas de Magnetita/química , Endossomos/química , Humanos , Lisossomos/química , Nanopartículas de Magnetita/ultraestrutura , Modelos Biológicos , Polímeros/químicaRESUMO
OBJECTIVES: Iron oxide nanoparticles have found prevalent applications in various fields including drug delivery, cell separation and as contrast agents. Super paramagnetic iron oxide (SPIO) nanoparticles allow researchers and clinicians to enhance the tissue contrast of an area of interest by increasing the relaxation rate of water. In this study, we evaluate the dependency of hydrodynamic size of iron oxide nanoparticles coated with Polyethylene glycol (PEG) on their relativities with 3 Tesla clinical MRI. MATERIALS AND METHODS: We used three groups of nanoparticles with nominal sizes 20, 50 and 100 nm with a core size of 8.86 nm, 8.69 nm and 10.4 nm that they were covered with PEG 300 and 600 Da. A clinical magnetic resonance scanner determines the T1 and T2 relaxation times for various concentrations of PEG-coated nanoparticles. RESULTS: The size measurement by photon correlation spectroscopy showed the hydrodynamic sizes of MNPs with nominal 20, 50 and 100 nm with 70, 82 and 116 nm for particles with PEG 600 coating and 74, 93 and 100 nm for particles with PEG 300 coating, respectively. We foud that the relaxivity decreased with increasing overall particle size (via coating thickness). Magnetic resonance imaging showed that by increasing the size of the nanoparticles, r2/r1 increases linearly. CONCLUSION: According to the data obtained from this study it can be concluded that increments in coating thickness have more influence on relaxivities compared to the changes in core size of magnetic nanoparticles.