NMR relaxivity of coated and non-coated size-sorted maghemite nanoparticles

ABSTRACT

The effect of polymer coating on MNR relaxometry of maghemite nanoparticles has been studied. The samples were carefully sorted by size in order to reach narrow size distribution (<0.2) with size ranging from 4.5 to 12.5?nm. Relaxation dispersion profile as well as studies at a fixed Larmor frequency, were recorded for numerous either uncoated or polymer coated samples. The NMR relaxivities r₁ and r₂ increase with nanoparticle diameter. We have analysed the role of polydispersity for nanoparticles with the same mean size on the dispersion curves. We have compared the role of coating on nanoparticles NMR relaxivity between bare and poly(sodium acrylate-co-maleate) coated nanoparticles. We have investigated the influence of nanoparticle size on the T₁ and T₂ activation energy Ea. While Ea decreases with nanoparticle diameter when determined from T₁, it increases from T₂ determination. The influence is more important for small particles (<9?nm) than for big particles (>9?nm). Moreover, the PAAMA coating changes the energy Ea obtained from T₂: Ea becomes independent of the nanoparticle diameter. These results highlight the need of a complete characterisation of the role of the coating on the relaxation of magnetic particles.     

HoF3 and DyF3 Nanoparticles as Contrast Agents for High‐Field Magnetic Resonance Imaging

Clinical contrast agents (CAs) currently used in magnetic resonance imaging (MRI) at low fields are less effective at high magnetic fields. The development of new CAs is mandatory to improve diagnostic capabilities of the new generation of high field MRI scanners. The purpose of this study is to synthesize uniform, water dispersible LnF₃ (Ln = Ho, Dy) nanoparticles (NPs) and to evaluate their relaxivity at high magnetic field (9.4 T) as a function of size and composition. Two different types of HoF₃ NPs are obtained by homogeneous precipitation in ethylene glycol at 120 °C. The use of holmium acetate as holmium precursor leads to rhombus‐like nanoparticles, while smaller, ellipsoid‐like nanoparticles are obtained when nitrate is used as the holmium salt. To explain this behavior, the mechanism of formation of both kinds of particles is analyzed in detail. Likewise, rhombus‐like DyF₃ nanoparticles are prepared following the same method as for the rhombus‐like HoF₃ nanoparticles. We have found, to the best of knowledge, the highest transverse relaxivity values at 9.4 T described in the literature for this kind of CAs. Finally, the LnF₃ NPs have shown negligible cytotoxicity for C6 rat glioma cells for concentrations up to 0.1 mg mL^?1.     

Facile Synthesis of Gd(OH)3‐Doped Fe3O4 Nanoparticles for Dual‐Mode T1‐ and T2‐Weighted Magnetic Resonance Imaging Applications

The facile hydrothermal synthesis of polyethyleneimine (PEI)‐coated iron oxide (Fe₃O₄) nanoparticles (NPs) doped with Gd(OH)₃ (Fe₃O₄‐Gd(OH)₃‐PEI NPs) for dual mode T₁‐ and T₂‐weighted magnetic resonance (MR) imaging applications is reported. In this approach, Fe₃O₄‐Gd(OH)₃‐PEI NPs are synthesized via a hydrothermal method in the presence of branched PEI and Gd(III) ions. The PEI coating onto the particle surfaces enables further modification of poly(ethylene glycol) (PEG) in order to render the particles with good water dispersibility and improved biocompatibility. The formed Fe₃O₄‐Gd(OH)₃‐PEI‐PEG NPs have a Gd/Fe molar ratio of 0.25:1 and a mean particle size of 14.4 nm and display a relatively high r₂ (151.37 × 10^?3m ^?1 s^?1) and r₁ (5.63 × 10^?3m ^?1 s^?1) relaxivity, affording their uses as a unique contrast agent for T₁‐ and T₂‐weighted MR imaging of rat livers after mesenteric vein injection of the particles and the mouse liver after intravenous injection of the particles, respectively. The developed Fe₃O₄‐Gd(OH)₃‐PEI‐PEG NPs may hold great promise to be used as a contrast agent for dual mode T₁‐ and T₂‐weighted self‐confirmation MR imaging of different biological systems.     

Ultrasmall iron oxide nanoparticles: Magnetic and NMR relaxometric properties

Ultrasmall iron oxide (USPIO) nanoparticles, with diameter mostly less than 3 nm dispersed in an organic carrier fluid were synthesized by polyol route. The evolution of ZFC-FC magnetization curves with temperature, as well as the shift of the ac susceptibility peaks upon changing the frequency, reveal that the nanoparticles in the fluid are non-interacting and superparamagnetic with the blocking temperature T_B ∼10 K. The Mössbauer spectra analysis proposed the core/shell structure of the nanoparticles consisting of stoichiometric γ-Fe₂O₃ core and non-stoichiometric shell. The nanoparticle surface layer has a great influence on their properties which is principally manifested in significant reduction of the magnetization and in a large increase in magnetic anisotropy. Magnetic moments do not saturate in fields up to 5 T, even at the lowest measured temperature, T = 5 K. The average magnetic particle diameter is changed from 1.3 to 1.8 nm with increasing magnetic field from 0 to 5 T which is noticeably smaller than the particle sizes measured by TEM. The estimated effective magnetic anisotropy constant value, K_eff = 2 × 10⁵ J/m³, is two orders of magnitude higher than in the bulk maghemite. Measurements of the longitudinal and transverse NMR relaxivity parameters on water diluted nanoparticle dispersions at 1.5 T gave the values r₁ = 0.028 mmol⁻¹ s⁻¹, r₂ = 0.050 mmol⁻¹ s⁻¹ and their ratio r₂/r₁ = 1.8. Continuous increase of the T₁-weighted MRI signal intensity with increasing Fe concentration in the nanoparticle dispersions was observed which makes this ferrofluid to behave as a positive T₁ contrast agent.     

Improved performance of silicon‐nanoparticle film‐coated dye‐sensitized solar cells

Silicon (Si) nanoparticles with average size of 13 nm and orange–red luminescence under UV absorption were synthesized using electrochemical etching of silicon wafers. A film of Si nanoparticles with thickness of 0.75 µm to 2.6 µm was coated on the glass (TiO₂ side) of a dye‐sensitized solar cell (DSSC). The cell exhibited nearly 9% enhancement in power conversion efficiency (η) at film thickness of ～2.4 µm under solar irradiation of 100 mW/cm² (AM 1.5) with improved fill factor and short‐circuit current density. This study revealed for the first time that the Si‐nanoparticle film converting UV into visible light and helping in homogeneous irradiation, can be utilized for improving the efficiency of the DSSCs. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Colloidal Flower‐Shaped Iron Oxide Nanoparticles: Synthesis Strategies and Coatings

The assembly of magnetic cores into regular structures may notably influence the properties displayed by a magnetic colloid. Here, key synthesis parameters driving the self‐assembly process capable of organizing colloidal magnetic cores into highly regular and reproducible multi‐core nanoparticles are determined. In addition, a self‐consistent picture that explains the collective magnetic properties exhibited by these complex assemblies is achieved through structural, colloidal, and magnetic means. For this purpose, different strategies to obtain flower‐shaped iron oxide assemblies in the size range 25–100 nm are examined. The routes are based on the partial oxidation of Fe(OH)₂, polyol‐mediated synthesis or the reduction of iron acetylacetonate. The nanoparticles are functionalized either with dextran, citric acid, or alternatively embedded in polystyrene and their long‐term stability is assessed. The core size is measured, calculated, and modeled using both structural and magnetic means, while the Debye model and multi‐core extended model are used to study interparticle interactions. This is the first step toward standardized protocols of synthesis and characterization of flower‐shaped nanoparticles.     

Polyacrylamide Nanoparticles with Visible and Near‐Infrared Autofluorescence

Nowadays, self‐fluorescent materials such as quantum dots are widely studied and applied in biomedical field. However, the biggest obstacle is biocompatibility. Here, a novel autofluorescent nanoparticle is constructed by crosslinking polyacrylamide nanoparticles (PAANPs) that contain ε‐poly‐l ‐lysine with glutaraldehyde (named fPAANPs). The nanoparticle has a mean size of about 16 nm, a zeta potential of about +16 mV, and strong visible and near‐infrared autofluorescence. The nanoparticle can be efficiently internalized into cells with high biocompatibility, the LC50 of which in RAW264.7, HepG2, and Hepa1‐6 cells is 6, 9, and 7.5 mg mL^?1, respectively. The nanoparticle shows no visible impact on the mice vitality even at a high intravenously administered dose (126 mg kg^?1). The autofluorescence of fPAANPs shows high stability, persistence, allowing long‐term dynamic imaging for 25 d in subcutaneous injections and 18 d in xenograft tumors in mice. The nanoparticle thus provides a self‐traceable nanomaterial that can be exploited as drug carrier and potential photodynamic therapy photosensitizer.     

Nonclassical Crystallization and Size Control of Ultra‐Small MoO2 Nanoparticles in Water

Size tuning for MoO₂ nanoparticles is demonstrated for the first time over a wide range 2–100 nm, through a colloidal route into water. A nucleation‐growth mechanism based on oriented attachment is evidenced to rationalize the impact of two simple synthetic levers: reactant ratio and temperature. The smallest non‐aggregated crystalline MoO₂ nanoparticles are reported, with specific surface area reaching 86 m² g^?1. Size and morphology control, along with the ability to produce, non‐aggregated ultra‐small MoO₂ particles are important for a wide range of applications, such as catalysis and energy storage. To exemplify the importance of size tuning, the impact of downscaling on the electrochemical properties in Li‐ion batteries is investigated.     

Micro‐Raman investigation of transition‐metal‐doped ZnO nanoparticles

We measured the Raman spectra of ZnO nanoparticles (ZnO‐NPs), as well as transition‐metal‐doped (5% Mn(II), Fe(II) or Co(II)) ZnO nanoparticles, with an average size of 9 nm. A typical Raman peak at 436 cm⁻¹ is observed in the ZnO‐NPs, whereas Zn_1−xMn_xO, Zn_1−xFe_xO and Zn_1−xCo_xO presented characteristic peaks at 661, 665 and 675 cm⁻¹, respectively. These peaks can be related to the formation of Mn₃O₄, Fe₃O₄ and Co₃O₄ species in the doped ZnO‐NPs. Moreover, these samples were analyzed at various laser powers. Here, we observed new vibrational modes (512, 571 and 528 cm⁻¹), which are specific to Mn, Fe and Co dopants, respectively, and ZnO‐NPs did not reveal any additional modes. The new peaks were interpreted either as disorder activated phonon modes or as local vibrations of Mn‐, Fe‐ and Co‐related complexes in ZnO. Copyright © 2007 John Wiley & Sons, Ltd.     

Nanoscale assembly of amine-functionalized colloidal iron oxide

We demonstrate a single-step facile approach for highly water-stable assembly of amine-functionalized Fe₃O₄ nanoparticles using thermal decomposition of Fe-chloride precursors in ethylene glycol medium in the presence of ethylenediamine. The average size of nanoassemblies is 40±1 nm, wherein the individual nanoparticles are about 6 nm. Amine-functionalized properties are evident from Fourier transform infrared spectrometer (FTIR), thermal and elemental analyses. The saturation magnetization and spin-echo r₂ of the nanoassemblies were measured to be 64.3 emu/g and 314.6 mM⁻¹ s⁻¹, respectively. The higher value of relaxivity ratio (r₂/r₁=143) indicates that nanoassemblies are a promising high-efficiency T2 contrast agent platform.     

Microwave-assisted synthesis of magnetite nanoparticles for MR blood pool contrast agents

Microwave-assisted polyol process was developed for the synthesis of magnetite nanoparticles with precisely controlled size, high crystallinity and high water solubility. The process is simple, time-saving and low energy-consuming due to the advantages of polyols and microwave irradiation combined. The crystal phases of the nanoparticles were determined by transmission electron microscopy, X-ray powder diffraction and Raman spectrum. The coating materials of the nanoparticles were analyzed by Fourier transformed infrared spectroscopy and thermal gravimetric analysis. Precise size tuning enables an easier way to adjust the relaxation properties of the magnetite nanoparticles. The colloid nanoparticles with high longitudinal relaxivity (r₁) and low ratio of transverse relaxivity (r₂) to r₁ have a potential application in magnetic resonance angiography.     

Amphiphilic Core–Shell Nanocomposite Particles for Enhanced Magnetic Resonance Imaging

A scalable synthesis of magnetic core–shell nanocomposite particles, acting as a novel class of magnetic resonance (MR) contrast agents, has been developed. Each nanocomposite particle consists of a biocompatible chitosan shell and a poly(methyl methacrylate) (PMMA) core where multiple aggregated γ‐Fe₂O₃ nanoparticles are confined within the hydrophobic core. Properties of the nanocomposite particles including their chemical structure, particle size, size distribution, and morphology, as well as crystallinity of the magnetic nanoparticles and magnetic properties were systematically characterized. Their potential application as an MR contrast agent has been evaluated. Results show that the nanocomposite particles have good stability in biological media and very low cytotoxicity in both L929 mouse fibroblasts (normal cells) and HeLa cells (cervical cancer cells). They also exhibited excellent MR imaging performance with a T₂ relaxivity of up to 364 mM_Fe^?1 s^?1. An in vivo MR test performed on a naked mouse bearing breast tumor indicates that the nanocomposite particles can localize in both normal liver and tumor tissues. These results suggest that the magnetic core–shell nanocomposite particles are an efficient, inexpensive and safe T₂‐weighted MR contrast agent for both liver and tumor MR imaging in cancer therapy.     

Temperature‐dependent,micro‐Raman spectroscopic study of barium titanate nanoparticles

A comparative, temperature‐dependent (80–500 K at 5 K intervals), micro‐Raman spectroscopic study of 300 and 50 nm diameter ceramic BaTiO₃ nanoparticles was carried out with the purpose of elucidating the nanoparticle size effect on the temperature dependence of the polar and non‐polar phonons. A method for calibrating Raman intensities, along with an iterative spectral fitting algorithm, is proposed for concurrent Raman band position and intensity analysis, increasing the analytical abilities of single temperature point Raman spectroscopy. The 300 nm particles exhibit all three phase transitions, whereas the 50 nm particles do not show evidence of these phase transitions in the same temperature range. The Curie temperature appears to be a phonon converging point, irrespective of the phonon symmetry. An attempt was made to qualitatively relate the temperature‐dependent Raman spectra to complimentary non‐spectroscopic methods, such as heat capacity and X‐ray diffraction studies. The study proves that the temperature‐dependent behavior of the polar phonon, 265 cm⁻¹, can be utilized as a sensitive phase transition probe. Copyright © 2014 John Wiley & Sons, Ltd.     

T1 and T2 relaxivities of succimer-coated MFe2O4 (M=Mn, Fe and Co) inverse spinel ferrites for potential use as phase-contrast agents in medical MRI

Superparamagnetic MFe₂³⁺O₄ (M=Mn²⁺, Fe²⁺ and Co²⁺) inverse spinel ferrite (ISF) nanoparticles with narrow size distribution having average diameters of 6-8 nm were synthesized by a diol reduction of organic metals and the surface was modified to be hydrophilic by coating with succimer. Magnetic resonance imaging (MRI) contrast enhancement by dipolar coupling defined interactions between the synthesized ISFs and protons in the bulk water was investigated with initial susceptibility, magnetization and anisotropy of the succimer-coated ISFs. The relaxivity ratios, r₂/r₁, for MnFe₂O₄, Fe₃O₄ and CoFe₂O₄ were measured to be 12.2, 23.1 and 62.3, respectively, which demonstrate the potential usefulness of these magnetic nanoparticles as T₂ contrast agents for MRI.     

High‐Strength Pressure‐Free Bonding Using Cu and Ni‐Sn Nanoparticles

High‐strength pressure‐free bonding is investigated using Cu nanoparticles as an alternative to conventional solders. Focus is placed on the morphology of Ni‐Sn intermetallic nanoparticles, an additive to a paste of Cu nanoparticles, for improvement of sinterability. The shear strength increases from 23.2 (Cu nanoparticles only) to 31.8 MPa, when 10 wt% of the newly synthesized 15‐nm Ni₃Sn₂ nanocubes is mixed with the Cu nanoparticle paste. This is the first example of the use of base metal nanoparticles under pressure‐free conditions to achieve the bonding strength of an ordinary Pb‐free solder (Sn‐Ag‐Cu). The addition of smaller Ni₃Sn₂ nanocubes 8 nm in size or irregularly shaped Ni₃Sn₂ nanoparticles (25.0 MPa) results in a limited increase in shear strength (26.6 MPa), while the addition of micrometer‐sized Ni₃Sn₂ particles results in a decrease in shear strength (21.5 MPa). The effects of the size and shape of the added Ni₃Sn₂ particles on the shear strength are discussed based on SEM observation of the sintered layers.     

Facile Synthesis of Manganese Tellurite Nanoparticles for Magnetic Resonance Imaging-Guided Photothermal Therapy

In this study, manganese tellurite (MnTeO₃) nanoparticles are developed as theranostic agents for magnetic resonance imaging (MRI)-guided photothermal therapy of tumor. MnTeO₃ nanoparticles are synthesized via a simple one-step method. The as-synthesized MnTeO₃ nanoparticles with uniform size show good biocompatibility. In particular, MnTeO₃ nanoparticles exhibit a high photothermal conversion efficiency (η = 26.3%), which is higher than that of gold nanorods. Moreover, MnTeO₃ nanoparticles also have high MRI performance. The longitudinal relaxivity (r₁) value of MnTeO₃ nanoparticles is determined to be 8.08 ± 0.2 mm ⁻¹ s⁻¹, which is higher than that of clinically approved T₁-contrast agents Gd-DTPA (4.49 ± 0.1 mm ⁻¹ s⁻¹). The subsequent MnTeO₃ nanoparticles-mediated photothermal therapy displays a highly efficient ablation of tumor cells both in vitro and in vivo with negligible toxicity. It is demonstrated that MnTeO₃ nanoparticles can serve as promising theranostic agents with great potentials for MRI-guided photothermal therapy.     

Particle size dependence of relaxivity for silica-coated iron oxide nanoparticles

We investigate the particle size dependence of the relaxivity of hydrogen protons in an aqueous solution of iron oxide (Fe₃O₄) nanoparticles coated in silica for biocompatibility. The T₁ and T₂ relaxation times for various concentrations of silica-coated nanoparticles were determined by a magnetic resonance scanner. We find that the relaxivity increased linearly with increasing particle size. The T₂ relaxivity (R₂) is more than 50 times larger than the T₁ relaxivity (R₁) for the nanoparticle contrast agent, which reflects the fact that the T₂ relaxation is mainly influenced by outer sphere processes. The high R₂/R₁ ratio demonstrates that silica-coated iron oxide nanoparticles may serve as a T₂ contrast agents in magnetic resonance imaging with high efficacy.     

Facile Synthesis of Lactobionic Acid‐Targeted Iron Oxide Nanoparticles with Ultrahigh Relaxivity for Targeted MR Imaging of an Orthotopic Model of Human Hepatocellular Carcinoma

Development of multifunctional nanoprobes for tumor diagnosis is extremely important in the field of molecular imaging. In this study, the facile synthesis of lactobionic acid (LA)‐targeted superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) with ultrahigh relaxivity for targeted magnetic resonance (MR) imaging of an orthotopic hepatocellular carcinoma (HCC) is reported. Polyethyleneimine (PEI)‐stabilized Fe₃O₄ NPs prepared via a mild reduction route are sequentially coupled with fluorescein isothiocyanate and polyethylene glycol‐LA (LA‐PEG‐COOH) segment, followed by acetylation of the remaining PEI surface amines. The formed LA‐targeted Fe₃O₄ NPs are thoroughly characterized. It is shown that the developed multifunctional LA‐targeted Fe₃O₄ NPs are colloidally stable and water‐dispersible, display an ultrahigh r ₂ relaxivity (579.89 × 10^?3 m ^?1 s^?1) and excellent hemocompatibility and cytocompatibility in the given concentration range, and can target HepG2 cells overexpressing asialoglycoprotein receptors as confirmed by in vitro cellular uptake assay, flow cytometry, and confocal microscopy. Most strikingly, the developed multifunctional LA‐targeted Fe₃O₄ NPs can be used as a nanoprobe for targeted MR imaging of HepG2 cells in vitro and an orthotopic tumor model of HCC in vivo. With the ultrahigh r ₂ relaxivity and the versatile PEI amine‐mediated conjugation chemistry, a range of different Fe₃O₄ NP‐based nanoprobes may be developed for theranostics of different types of cancer.     

Docetaxel‐Loaded Nanoparticles of Dendritic Amphiphilic Block Copolymer H40‐PLA‐b‐TPGS for Cancer Treatment

A dendritic amphiphilic block copolymer H40‐poly(d,l ‐lactide)‐block‐d‐α‐tocopheryl polyethylene glycol 1000 succinate (H40‐PLA‐b‐TPGS) is synthesized, which is then employed to develop a system of nanoparticles (NPs) loaded with docetaxel (DTX) as a model drug for cancer treatment due to its higher drug‐loading content and drug encapsulation efficiency, smaller particle size, faster drug release, and higher cellular uptake in comparison to the linear PLA polymer NPs and PLA‐b‐TPGS copolymer NPs. The drug‐loaded NPs are prepared by a modified nanoprecipitation method and characterized in terms of size and size distribution, surface morphology, drug release profile, and physical state of DTX. Cellular uptake of coumarin 6‐loaded NPs by MCF‐7 cancer cells is determined by flow cytometry and confocal laser scanning microscopy. The antitumor efficacy of the drug‐loaded NPs is investigated in vitro by MTT assay and in vivo by xenograft tumor model. The 72 h IC50 of the drug formulated in the PLA, PLA‐b‐TPGS, and H40‐PLA‐b‐TPGS NPs is found to be, 1.5 ± 0.3, 0.9 ± 0.1, and 0.15 ± 0.06 μg mL^?1, which are 7.3, 12.2, and 73.3‐fold effective than 11.0 ± 1.2 μg mL^?1 for Taxotere, respectively. Such advantages are further confirmed by the measurement of the tumor size and weight.     

Hydrothermal synthesis and magnetic properties of CuSb<Subscript>2</Subscript>O<Subscript>6</Subscript> nanoparticles and nanorods

Nanoparticles and nanorods of CuSb₂O₆ are prepared by hydrothermal method and its high temperature α-phase is stabilized at room temperature. The average size of the nanoparticles is ca. 13.7 nm. The nanorods, with a width of ca. 20 nm and an aspect ratio of ca. 5, are the agglomerates composing of smaller nanoparticles with an average size of ca. 8.3 nm. Compared with the high temperature α-phase of bulk sample at 400 K, the lattice of nanophases elongated in ab plane and compressed along c direction. The CuSb₂O₆ nanoparticles exhibit predominant paramagnetic phenomenon. The difference in magnetic properties of the nanoparticles and nanorods indicates the interfacial interaction of agglomerated nanoparticles.