Synthesis, Surface Modification and Magnetic Properties Analysis of Heat-Generating Cobalt-Substituted Magnetite Nanoparticles.

Here, we present the results of the synthesis, surface modification, and properties analysis of magnetite-based nanoparticles, specifically Co0.047Fe2.953O4 (S1) and Co0.086Fe2.914O4 (S2). These nanoparticles were synthesized using the co-precipitation method at 80 °C for 2 h. They exhibit a single-phase nature and crystallize in a spinel-type structure (space group Fd3¯m). Transmission electron microscopy analysis reveals that the particles are quasi-spherical in shape and approximately 11 nm in size. An observed increase in saturation magnetization, coercivity, remanence, and blocking temperature in S2 compared to S1 can be attributed to an increase in magnetocrystalline anisotropy due to the incorporation of Co ions in the crystal lattice of the parent compound (Fe3O4). The heating efficiency of the samples was determined by fitting the Box-Lucas equation to the acquired temperature curves. The calculated Specific Loss Power (SLP) values were 46 W/g and 23 W/g (under HAC = 200 Oe and f = 252 kHz) for S1 and S2, respectively. Additionally, sample S1 was coated with citric acid (Co0.047Fe2.953O4@CA) and poly(acrylic acid) (Co0.047Fe2.953O4@PAA) to obtain stable colloids for further tests for magnetic hyperthermia applications in cancer therapy. Fits of the Box-Lucas equation provided SLP values of 21 W/g and 34 W/g for CA- and PAA-coated samples, respectively. On the other hand, X-ray photoelectron spectroscopy analysis points to the catalytically active centers Fe2+/Fe3+ and Co2+/Co3+ on the particle surface, suggesting possible applications of the samples as heterogeneous self-heating catalysts in advanced oxidation processes under an AC magnetic field.

Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors.

As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (177Lu), generating 177Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of 177Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the 177Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, 177Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy.

Self-Heating Flower-like Nanoconstructs with Limited Incorporation of Yttrium in Maghemite: Effect of Chemical Composition on Heating Efficiency, Cytotoxicity and Genotoxicity.

Partial cation substitution can significantly change the physical properties of parent compounds. By controlling the chemical composition and knowing the mutual relationship between composition and physical properties, it is possible to tailor the properties of materials to those that are superior for desired technological application. Using the polyol synthesis procedure, a series of yttrium-substituted iron oxide nanoconstructs, γ-Fe2-xYxO3 (YIONs), was prepared. It was found that Y3+ could substitute Fe3+ in the crystal structures of maghemite (γ-Fe2O3) up to a limited concentration of ~1.5% (γ-Fe1.969Y0.031O3). Analysis of TEM micrographs showed that crystallites or particles were aggregated in flower-like structures with diameters from 53.7 ± 6.2 nm to 97.3 ± 37.0 nm, depending on yttrium concentration. To be investigated for potential applications as magnetic hyperthermia agents, YIONs were tested twice: their heating efficiency was tested and their toxicity was investigated. The Specific Absorption Rate (SAR) values were in the range of 32.6 W/g to 513 W/g and significantly decreased with increased yttrium concentration in the samples. Intrinsic loss power (ILP) for γ-Fe2O3 and γ-Fe1.995Y0.005O3 were ~8-9 nH·m2/Kg, which pointed to their excellent heating efficiency. IC50 values of investigated samples against cancer (HeLa) and normal (MRC-5) cells decreased with increased yttrium concentration and were higher than ~300 µg/mL. The samples of γ-Fe2-xYxO3 did not show a genotoxic effect. The results of toxicity studies show that YIONs are suitable for further in vitro/in vivo studies toward to their potential medical applications, while results of heat generation point to their potential use in magnetic hyperthermia cancer treatment or use as self-heating systems for other technological applications such as catalysis.

Electrochemical Determination of Morphine in Urine Samples by Tailoring FeWO4/CPE Sensor.

Morphine (MORPH) is natural alkaloid and mainly used as a pain reliever. Its monitoring in human body fluids is crucial for modern medicine. In this paper, we have developed an electrochemical sensor for submicromolar detection of MORPH. The sensor is based on modified carbon paste electrode (CPE) by investigating the FexW1-xO4 ratio in iron tungstate (FeWO4), as well as the ratio of this material in CPE. For the first time, the effect of the iron-tungsten ratio in terms of achieving the best possible electrochemical characteristics for the detection of an important molecule for humans was examined. Morphological and electrochemical characteristics of materials were studied. The best results were obtained using Fe1W3 and 7.5% of modifier in CPE. For MORPH detection, square wave voltammetry (SWV) was optimized. Under the optimized conditions, Fe1W3@CPE resulted in limit of detection (LOD) of the method of 0.58 µM and limit of quantification (LOQ) of 1.94 µM. The linear operating range between 5 and 85 µM of MORPH in the Britton-Robinson buffer solution (BRBS) at pH 8 as supporting electrolyte was obtained. The Fe1W3@CPE sensor resulted in good selectivity and excellent repeatability with relative standard deviation (RSD) and was applied in real-world samples of human urine. Application for direct MORPH detection, without tedious sample pretreatment procedures, suggests that developed electrochemical sensor has appeared to be a suitable competitor for efficient, precise, and accurate monitoring of the MORPH in biological fluids.

Design and preparation of proline, tryptophan and poly-l-lysine functionalized magnetic nanoparticles and their radiolabeling with 131I and 177Lu for potential theranostic use.

Surface modification of magnetic nanoparticles with poly-l-lysine, proline, and tryptophan was used to design potential theranostic agents for the application in cancer diagnosis and radionuclide-hyperthermia therapy. Characterization of bare and functionalized magnetic nanoparticles was performed in detail. The transparency of the examined magnetic nanoparticles was measured in the non-alternating magnetic field for a complete and better understanding of hyperthermia. For the first time amino acid-functionalized magnetic nanoparticles were labeled with theranostic radionuclides 131I and 177Lu. The specific absorption rate (SAR) procured for poly-l-lysine functionalized magnetic nanoparticles (SAR values of 99.7 W/g at H0 = 15.9 kA/m and resonant frequency of 252 kHz) demonstrated their possible application in magnetic hyperthermia. Poly-l-lysine functionalized magnetic nanoparticles labeled with 177Lu showed the highest radiochemical purity (>99.00 %) and in vitro stability in saline and serum (>98.00 % up to 96 h). The in vivo analysis performed after their intravenous administration in healthy Wistar rats presented good in vivo stability for several days. Encouraging results as well as magnetic and radiochemical properties of 177Lu-PLL-MNPs (80 °C) justify their further testing toward the potential use as theranostic agents for diagnostic and combined radionuclide-hyperthermia therapeutic applications.

Voltammetric immunoassay based on MWCNTs@Nd(OH)3-BSA-antibody platform for sensitive BSA detection.

An electrochemical approach is presented based on multiwall carbon nanotubes (MWCNTs) and neodymium(III) hydroxide (Nd(OH)3) nanoflakes for detection of bovine serum albumin (BSA). The materials were characterized morphologically (XRPD, SEM, and HR-TEM) and electrochemically (DPV, EIS). The MWCNTs@Nd(OH)3 composite was used as support for bovine serum albumin polyclonal antibody (anti-BSA). After the antibody immobilization on the electrochemical platform and antigen/antibody binding time (optimum 60 min), the proposed approach shows a linear voltammetric response toward BSA concentration in the range 0.066 to 6.010 ng mL-1 at maximum peak potential of 0.13 V (vs. Ag/AgCl). Limit of detection (LOD) and limit of quantification (LOQ) were 18 pg mL-1 and 61 pg mL-1, respectively. The precision of the method calculated as relative standard deviation (RSD) of five independent measurements was better 3%. The selectivity of the optimized method regarding structurally similar proteins (human serum albumin and human hemoglobin), ions (Na+, K+, Ca2+, and NO2-), or compounds (glucose, ascorbic acid, dopamine, uric acid, paracetamol, and glycine) was found to be satisfactory, with the current changes of less than 5% in the presence of up to 1 × 105 times higher concentrations (depending on the compound) of the listed potential interfering compounds. Practical applicability of immunosensor for BSA determination in cow whey sample, with recovery values in the range 97 to 103%, shows that the developed method has high potential for precise and accurate detection of BSA, as well as exceptional miniaturization possibilities for on-site and equipment-free sensing.

90Y-CA/SPIONs for dual magnetic hyperthermia-radionuclide nanobrachytherapy of solid tumours.

Radiolabelled superparamagnetic iron oxide nanoparticles (SPIONs) are a promising nanomaterial for the development of dual radiation/hyperthermia cancer therapy. To that purpose, flower-shaped SPIONs with an exceptional heating capability were synthesised and coated with citrate, dextran or (3-aminopropyl)triethoxysilane. Both non-coated and coated SPIONs were nontoxic to CT-26 mouse colon cancer cells up to 1.0 mg ml-1in vitro. In an oscillating magnetic field, citrate-coated SPIONs (CA/SPIONs) displayed the highest heating rate (SAR âˆ¼ 253 W g-1) and the strongest hyperthermia effects against CT-26 cells. Labelling of the CA/SPIONs by the90Y radionuclide, emitting ß-radiation with an average/maximum energy of 0.94/2.23 MeV, and deep tissue penetration generated90Y-CA/SPIONs intended for the therapy of solid tumours. However, intravenous injection of90Y-CA/SPIONs in CT-26 xenograft-bearing mice resulted in low tumour accumulation. On the contrary, intratumoural injection resulted in long-term retention at the injection site. A single intratumoural injection of 0.25 mg CA/SPIONs followed by 30-min courses of magnetic hyperthermia for four consecutive days caused a moderate antitumour effect against CT-26 and 4T1 mouse tumour xenografts. Intratumoural application of 1.85 MBq/0.25 mg90Y-CA/SPIONs, alone or combined with hyperthermia, caused a significant (P ≤ 0.01) antitumour effect without signs of systemic toxicity. The results confirm the suitability of90Y-CA/SPIONs for monotherapy or dual magnetic hyperthermia-radionuclide nanobrachytherapy (NBT) of solid tumours.

Aminosilanized flower-structured superparamagnetic iron oxide nanoparticles coupled to 131I-labeled CC49 antibody for combined radionuclide and hyperthermia therapy of cancer.

Combined radionuclide therapy with magnetic nanoparticles-mediated hyperthermia has been under research focus as a promising tumor therapy approach. The objective of this study was to investigate the potential of 131I-radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) prepared as the ~40 nm flower-shaped structures with excellent heating efficiency (specific absorption rate at H0 = 15.9 kA∙m-1 and resonant frequency of 252 kHz was 123.1 W∙g-1) for nano-brachytherapy of tumors. 131I-radiolabeled CC49 antibody attached to SPIONs via reactive groups of 3-aminopropyltriethoxysilane (APTES) provided specificity and long-lasting localized retention after their intratumoral application into LS174T human colon adenocarcinoma xenografts in NOD-SCID mice. The results demonstrate feasibility and effectiveness of magnetic hyperthermia (HT), radionuclide therapy (RT) and their combination (HT + RT) in treating cancer in xenograft models. Combined therapy approach induced a significant (p < 0.01) tumor growth suppression in comparison to untreated groups presented by the tumor volume inhibitory rate (TVIR): 54.38%, 68.77%, 73.00% for HT, RT and HT + RT, respectively in comparison to untreated group and 48.31%, 64,62% and 69,41%, respectively, for the SPIONs-only injected group. Histopathology analysis proved the necrosis and apoptosis in treated tumors without general toxicity. Obtained data support the idea that nano-brachytherapy combined with hyperthermia is a promising approach for effective cancer treatment.

99mTc-, 90Y-, and 177Lu-Labeled Iron Oxide Nanoflowers Designed for Potential Use in Dual Magnetic Hyperthermia/Radionuclide Cancer Therapy and Diagnosis.

Development of a complex based on iron oxide nanoparticles (IONPs) for diagnosis and dual magnetic hyperthermia/radionuclide cancer therapy accomplishing high yields of radiolabeling and great magnetic heat induction is still a challenge. We report here the synthesis of citric acid, poly(acrylic acid) (PAA) and poly(ethylene glycol) coated IONPs and their labeling with three radionuclides, namely, technetium (99mTc), yttrium (90Y), and lutetium (177Lu), aiming at potential use in cancer diagnosis and therapy. Polyol-synthesized IONPs are a flowerlike structure with 13.5 nm spherically shaped cores and 24.8 nm diameter. PAA-coated nanoparticles (PAA@IONP) showed the best characteristics such as easy radiolabeling with very high yields (>97.5%) with all three radionuclides, and excellent in vitro stabilities with less than 10% of radionuclides detaching after 24 h. Heating ability of PAA@IONP in an alternating external magnetic field showed intrinsic loss power value of 7.3 nH m2/kg, which is one of higher reported values. Additionally, PAA@IONP itself presented no significant cytotoxicity to the CT-26 cancer cells, reaching IC50 at 60 µg/mL. However, under the external magnetic field, they show hyperthermia-mediated cells killing, which correlated with the magnetic field strength and time of exposure. Since PAA@IONP are easy to prepare, biocompatible, and with excellent magnetic heat induction, these nanoparticles radiolabeled with high-energy beta emitters 90Y and 177Lu have valuable potential as agent for dual magnetic hyperthermia/radionuclide therapy, while radiolabeled with 99mTc could be used in diagnostic imaging.

Differently shaped nanocrystalline (Fe, Y)3O4 and its adsorption efficiency toward inorganic arsenic species.

Herein we report effects of partial substitution of Fe3+ by Y3+ in magnetite (Fe3O4) on morphology and inorganic arsenic species adsorption efficiency of the Fe3-x Y x O4 nanoparticles formed. The series of Fe3-x Y x O4 (x = 0.00, 0.042 and 0.084, labeled as Y00, Y05 and Y10, respectively) was synthesized using co-precipitation followed by microwave-hydrothermal treatment (MW) at 200 °C. With increase of yttrium content (x value), both the morphological inhomogeneity of the samples and the fraction of spinel nanorods as compared to spinel pseudospherical particles increased. By both transmission electron microscopy and x-ray powder diffraction analyses, it was determined that the direction of growth of the spinel nanorods is along the [110] crystallographic direction. The Fe3-x Y x O4 affinities of adsorption toward the inorganic arsenic species, As(III) (arsenite, AsO3 3-) and As(V) (arsenate, AsO4 3-), were investigated. Increased Y3+ content related to changes in sample morphology was followed by a decrease of As(III) removal efficiency and vice versa for As(V). The increase in Y3+ content, in addition to increasing the adsorption capacity for As(V), significantly expanded the optimum pH range for the maximum removal and decreased the contact time for necessary 50% removal (t 1/2) of As(V) (Y00: pH 2-3, t 1/2 = 3.12 min; Y05: pH 2-6, t 1/2 = 2.12 min and Y10: pH 2-10, t 1/2 = 1.12 min). The results point to incorporation of Y3+ in the crystal lattice of magnetite, inducing nanorod spinel structure formation with significant changes in sorption properties important for the removal of inorganic arsenic from waters.

Point-of-care amperometric determination of L-dopa using an inkjet-printed carbon nanotube electrode modified with dandelion-like MnO2 microspheres.

An electrochemical sensor is described for the determination of L-dopa (levodopa; 3,4-dihydroxyphenylalanine). An inkjet-printed carbon nanotube (IJPCNT) electrode was modified with manganese dioxide microspheres by drop-casting. They coating was characterized by field emission scanning electron microscopy, Fourier-transform infrared spectroscopy and X-ray powder diffraction. The sensor, best operated at a working voltage of 0.3 V, has a linear response in the 0.1 to 10 µM L-dopa concentration range, a 54 nM detection limit, excellent reproducibility, repeatability and selectivity. The amperometric approach was applied to the determination of L-dopa in spiked biological fluids and displayed satisfactory accuracy and precision. Graphical abstract Schematic representation of an amperometric method for determination L-dopa. It is based on the use of inkjet-printed carbon nanotube electrode (IJPCNT) modified with manganese dioxide (MnO2).

99mTc-bisphosphonate-coated magnetic nanoparticles as potential theranostic nanoagent.

Novel theranostic nanoplatform is expected to integrate imaging for guiding and monitoring of the tumor therapy with great therapeutic efficacy and fewer side effects. Here we describe the preparation of a multifunctional 99mTc-bisphosphonate-coated magnetic nanoparticles (MNPs) based on Fe3O4 and coated with two hydrophilic bisphosphonate ligands, i.e., methylene diphosphonate (MDP) and 1-hydroxyethane-1,1- diphosphonate (HEDP). The presence of the bisphosphonates on the MNPs surface, enabled their biocompatibility, colloidal stability and successful binding of the radionuclide. The morphology, size, structure, surface charge and magnetic properties of obtained bisphosphonate-coated Fe3O4 MNPs were characterized by transmission electron microscopy, X-ray powder diffraction, dynamic light scattering, laser Doppler electrophoresis, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The specific power absorption values for Fe3O4-MDP and Fe3O4-HEDP were 113 W/g and 141 W/g, respectively, indicated their heating ability under applied magnetic field. Coated MNPs were radiolabeled with 99mTc using stannous chloride as the reducing agent in a reproducible high yield (95% for Fe3O4-MDP and 97% for Fe3O4-HEDP MNPs) and were remained stable in saline and human serum for 24 h. Ex vivo biodistribution studies presented significant liver and spleen uptake in healthy Wistar rats after intravenous administration at all examined time points due to the colloidal nature of both 99mTc-MNPs. Results of scintigraphy studies are in accordance with ex vivo biodistribution studies, demonstrating high in vivo stability of radiolabeled MNPs and therefore results of both methods were proved as accurate information on the biodistribution profile of investigated MNPs. Overall, in vitro and in vivo stability as well as heating ability, indicate that biocompatible radiolabeled bisphosphonate magnetic nanoparticles exhibit promising potential as a theranostic nanoagent.

Enhancing Analytical Performance of (Mg,Fe)3O4/Glassy Carbon Electrodes by Tailoring Chemical Composition of (Mg,Fe)3O4 Nanoparticles.

A series of MgxFe3-xO4 (x ═ 0-1) nanoparticles was synthesized in order to prepare novel MgxFe3-xO4/glassy carbon modified electrodes. Effects of magnesium content (x) on the analytical performance of the modified electrodes in the detection of gallic acid were evaluated. It was found that magnesium concentration and crystallite/particle size of the prepared nanoparticles play significant roles in the sensing properties of modified electrodes. The increase of magnesium concentration up to the value of x ═ 0.4 in MgxFe3-xO4/glassy carbon paste was accompanied by an increase of the corresponding oxidation current of gallic acid. However, further growth of x value caused decline of the obtained oxidation current. An electroanalytical procedure was established, and the analytical performance of the proposed Mg0.4Fe2.6O4/glassy carbon paste electrode was monitored using previously optimized experimental conditions. A working linear range from 1-39 µM gallic acid was obtained with detection limit of 0.29 µM. According to these results, the developed procedure can be applied for detection of low concentrations of gallic acid with satisfactory selectivity in the presence of some common naturally occurring compounds. Experimental results indicate that the developed procedure could be a novel approach in the detection of antioxidant, overcoming some known disadvantages such as passivation, and could be a promising replacement for sophisticated chromatographic methods.

RuO2/graphene nanoribbon composite supported on screen printed electrode with enhanced electrocatalytic performances toward ethanol and NADH biosensing.

In this work, we aimed to propose a newly synthesized composite material with enhanced electrocatalytic properties as a novel screen-printed sensor for the quantification of NADH. Additionally, the surface was modified with alcohol dehydrogenase for the preparation of an amperometric biosensor for analysis of ethanol. Synthesized material was characterized using several microstructural (FE-SEM, HR-TEM, XRD) and electrochemical (CV, EIS) techniques. The electrochemical response of the tested analytes was investigated as a function of important parameters. Under optimal conditions, the working linear range and limit of detection for ethanol sensing was 1-1800 µM and 0.19 µM, respectively. For NADH, the linear range was from 1 to 1300 µM with limit of detection of 0.52 µM. Moreover, effects of some possible interfering compounds were investigated and the developed procedure was applied to commercial alcoholic beverages. The results obtained showed satisfactory precision and accuracy of the developed method and confirm the proposed approach could be a possible replacement for the currently used techniques for ethanol and NADH quantification.

Design of titanium nitride- and wolfram carbide-doped RGO/GC electrodes for determination of gallic acid.

In the present paper, the electrochemical behavior and the properties of two modified glassy carbon (GC) electrodes used for quantification of gallic acid in sweet wines were compared. A comparative study was conducted between titanium nitride- or wolfram carbide-doped reduced graphene oxide, labeled as TNrGO and WCrGO, respectively, modified GC electrodes, which are promising composite nanomaterials for electroanalytical applications. For the first time, WCrGO was synthesized and its electroanalytical properties compared with those of TNrGO. Results showed that the proposed materials exhibited enhanced characteristics, e.g., low limits of detection (1.1 µM and 3.1 µM for TNrGO and WCrGO, respectively), wide linear ranges (for TNrGO 4.5-76 µM and for WCrGO 10-100 µM), low adsorption, and low background current, which make them promising candidates for electrochemical sensing applications.

Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles.

Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in the MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er)3O4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6-7nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90K. Reduction in saturation magnetization due to incorporation of 1.7% Er3+ into the Fe3O4 matrix was clearly observed. From the biological standpoint, citric acid coated (Fe,Er)3O4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish (Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er)3O4 MNPs could be further considered for the potential application as a diagnostic and/or therapeutic agent. This work also demonstrates that combined application of these techniques is a promising tool for studies of pharmacokinetics of the new MNPs in complex biological systems.

Design and preparation of 90Y-labeled imidodiphosphate- and inositol hexaphosphate-coated magnetic nanoparticles for possible medical applications.

Radiolabeled magnetic nanoparticles (MNPs) coated with hydrophilic phosphate ligands, i.e., imidodiphosphate (IDP) and inositol hexaphosphate (IHP), were developed as multifunctional agents to localize both radioactivity and magnetic energy at a tumor site. The coating of MNPs with phosphates made them biocompatible, increased their colloidal stability and allowed binding of the radionuclide 90Y to the available functional groups on the surface of the MNPs. IDP and IHP have not hitherto been used for the coating of MNPs and the results of this study of the functionalized MNPs showed that the phosphate groups influenced the modification of the surface of MNPs. Characterization of the MNPs was performed using X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering and laser Doppler electrophoresis. The specific power absorption values obtained for MNPs (46.95-80.76 W g-1) in different physiological media indicated their possible application in hyperthermia treatment. Both types of coated MNPs were 90Y-labeled in a reproducible high yield (>98%). In vitro studies of 90Y-MNPs in saline and human serum showed their high stability after 72 h. The biodistribution pattern of the MNPs after intravenous administration to healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-Fe3O4-IDP and 90Y-Fe3O4-IHP MNPs were predominantly found in the liver (85.21% ID and 86.22% ID), followed by the spleen (9.23% ID and 8.82% ID) and the lungs (1.53% ID and 1.53% ID). The results of this comprehensive study showed that radiolabeled biocompatible phosphate magnetic complexes hold great promise for therapeutic uses combining magnetic hyperthermia and radiotherapy.

Gallium-68 Labeled Iron Oxide Nanoparticles Coated with 2,3-Dicarboxypropane-1,1-diphosphonic Acid as a Potential PET/MR Imaging Agent: A Proof-of-Concept Study.

The aim of this study was to develop a dual-modality PET/MR imaging probe by radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized with water soluble stabilizer 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), with the positron emitter Gallium-68. Magnetite nanoparticles (Fe3O4 MNPs) were synthesized via coprecipitation method and were stabilized with DPD. The Fe3O4-DPD MNPs were characterized based on their structure, morphology, size, surface charge, and magnetic properties. In vitro cytotoxicity studies showed reduced toxicity in normal cells, compared to cancer cells. Fe3O4-DPD MNPs were successfully labeled with Gallium-68 at high radiochemical purity (>91%) and their stability in human serum and in PBS was demonstrated, along with their further characterization on size and magnetic properties. The ex vivo biodistribution studies in normal Swiss mice showed high uptake in the liver followed by spleen. The acquired PET images were in accordance with the ex vivo biodistribution results. Our findings indicate that 68Ga-Fe3O4-DPD MNPs could serve as an important diagnostic tool for biomedical imaging.

Preparation and in vivo evaluation of multifunctional 9°Y-labeled magnetic nanoparticles designed for cancer therapy.

Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe3O4-Naked (80 ± 5 nm) and polyethylene glycol 600 diacid functionalized Fe3O4(Fe3O4-PEG600) MNPs (46 ± 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe3O4-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of (90) Y-MNPs were compared. Both types of MNPs were (90)Y-labeled in reproducible high yield (>97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for (90)Y-Fe3O4-Naked MNPs and 19.61%ID/g for (90)Y-Fe3O4-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of (90)Y-Fe3O4-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for (90)Y-Fe3O4-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as (90)Y-Fe3O4-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy.

An integrated study of thermal treatment effects on the microstructure and magnetic properties of Zn-ferrite nanoparticles.

The evolution of the magnetic state, crystal structure and microstructure parameters of nanocrystalline zinc-ferrite, tuned by thermal annealing of ∼4 nm nanoparticles, was systematically studied by complementary characterization methods. Structural analysis of neutron and synchrotron x-ray radiation data revealed a mixed cation distribution in the nanoparticle samples, with the degree of inversion systematically decreasing from 0.25 in an as-prepared nanocrystalline sample to a non-inverted spinel structure with a normal cation distribution in the bulk counterpart. The results of DC magnetization and Mössbauer spectroscopy experiments indicated a superparamagnetic relaxation in ∼4 nm nanoparticles, albeit with different freezing temperatures T(f) of 27.5 K and 46 K, respectively. The quadrupole splitting parameter decreases with the annealing temperature due to cation redistribution between the tetrahedral and octahedral sites of the spinel structure and the associated defects. DC magnetization measurements indicated the existence of significant interparticle interactions among nanoparticles ('superspins'). Additional confirmation for the presence of interparticle interactions was found from the fit of the T(f)(H) dependence to the AT line, from which a value of the anisotropy constant of K(eff) = 5.6 × 10(5) erg cm(-3) was deduced. Further evidence for strong interparticle interactions was found from AC susceptibility measurements, where the frequency dependence of the freezing temperature T(f)(f) was satisfactory described by both Vogel-Fulcher and dynamic scaling theory, both applicable for interacting systems. The parameters obtained from these fits suggest collective freezing of magnetic moments at T(f).