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.     

Dextran‐Coated Antiferromagnetic MnO Nanoparticles for a T1‐MRI Contrast Agent with High Colloidal Stability

A simple approach to synthesize carboxymethyl dextran‐coated MnO nanoparticles (CMDex‐MnONPs) with high colloidal stability in physiological saline solutions is described here for potential applications as a magnetic resonance imaging (MRI) T₁ contrast agent. The thermal decomposition methodology is used to produce uniform MnONPs with an average size of around 20 nm, and its hydrophobic surface is modified with CMDex molecules, conferring hydrophilic properties. After CMDex coating, the nanoparticle presents high colloidal stability in concentrations ranging from 10 to 50 μg mL^?1, average hydrodynamic size (Z‐average) of 130 nm, polydispersity degree of ≈12%, and negative surface charge in both simulated body fluid solutions and pure water with zeta‐potential of –20 and –40 mV, respectively. The CMDex‐MnONPs with 20 nm show antiferromagnetic behavior at room temperature, and the magnetic properties are found to be strongly dependent of the nanoparticle size, increasing the contribution of the ferromagnetic Mn₃O₄ phase with decreasing size for nanoparticles about 3 nm. Cytotoxicity evaluation in cancerous and noncancerous cells in the range of 5.0–50.0 μg mL^?1 shows low toxicity for cancerous cells and lack of the same for healthy cells lines. Related to the magnetic properties, CMDex‐MnONP presents significant r₁ relaxivity and low r₂/r₁ relaxivity ratio. The results suggest that these nanoparticles display characteristics for potential applications as an MRI T₁ contrast agent.     

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.     

Multifunctional core–shell nanoparticles: superparamagnetic,mesoporous, and thermosensitive

Multifunctional core–shell composite nanoparticles (NPs) have been developed by the combination of three functionalities into one entity, which is composed of a single Fe₃O₄ NP as the magnetic core, mesoporous silica (mSiO₂) with cavities as the sandwiched layer, and thermosensitive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAAm-co-AAm)) copolymer as the outer shell. The mSiO₂-coated Fe₃O₄ NPs (Fe₃O₄@mSiO₂) are monodisperse and the particle sizes were varied from 25 to 95 nm by precisely controlling the thickness of mSiO₂-coating layer. The P(NIPAAm-co-AAm) were then grown onto surface-initiator-modified Fe₃O₄@mSiO₂ NPs through free radical polymerization. These core–shell composite NPs (designated as Fe₃O₄@mSiO₂@P(NIPAAm-co-AAm)) were found to be superparamagnetic with high r ₂ relaxivity. To manipulate the phase transition behavior of these thermosensitive polymer-coated NPs for future in vivo applications, the characteristic lower critical solution temperature (LCST) was subtly tuned by adjusting the composition of the monomers to be around the human body temperature (i.e. 37 °C), from ca. 34 to ca. 42 °C. The thermal response of the core–shell composite NPs to the external magnetic field was also demonstrated. Owing to their multiple functionality characteristics, these porous superparamagnetic and thermosensitive NPs may prove valuable for simultaneous magnetic resonance imaging (MRI), temperature-controlled drug release, and temperature-programed magnetic targeting and separation applications.     

Magnetic,optical and relaxometric properties of organically coated gold–magnetite (Au–Fe3O4) hybrid nanoparticles for potential use in biomedical applications

We present the magnetic, optical and relaxometric properties of multifunctional Au–Fe₃O₄ hybrid nanoparticles (HNPs), as possible novel contrast agents (CAs) for magnetic resonance imaging (MRI). The HNPs have been synthesized by wet chemical methods in heterodimer and core–shell geometries and capped with oleylamine. Structural characterization of the samples have been made by X-ray diffraction and transmission electron microscopy, while magnetic properties have been investigated by means of Superconducting Quantum Interference Device-SQUID magnetometry experiments. As required for MRI applications using negative CAs, the samples resulted superparamagnetic at room temperature and well above their blocking temperatures. Optical properties have been investigated by analyzing the optical absorbtion spectra collected in UV–visible region. Relaxometric measurements have been performed on organic suspensions of HNPs and Nuclear Magnetic Resonance (NMR) dispersion curves have been obtained by measuring the longitudinal 1/T₁ and transverse 1/T₂ relaxation rates of solvent protons in the range 10 kHz/300 MHz at room temperature. NMR relaxivities r₁ and r₂ have been compared with ENDOREM^®, one of the commercial superparamagnetic iron oxide based MRI contrast agents. MRI contrast enhancement efficiencies have been investigated also by examining T₂-weighted MR images of suspensions. The experimental results suggest that the nanoparticles' suspensions are good candidates as negative CAs.     

Highly Acid‐Resistant,Magnetically Steerable Acoustic Micromotors Prepared by Coating Gold Microrods with Fe3O4 Nanoparticles via pH Adjustment

There is mounting interest in designing magnetically steerable nano‐ and micromotors for next generation medical nanorobotics, which requires biocompatibility for each individual component. Although various magnetic materials (e.g., Ni, Co, and Fe₃O₄) have been incorporated into micromotors, their acid resistance remains largely unexplored. In this article, a simple one‐step method to prepare magnetic microrods via electrostatic attraction between paramagnetic magnetite nanoparticles (Fe₃O₄ NPs) and gold microrods at appropriate pH values is reported. The as‐prepared Fe₃O₄‐coated micromotors can be powered by MHz ultrasound and easily steered by external magnetic fields, and perform well in harsh working conditions such as high acidity, high viscosity, and high ionic strength. In particular, extended exposure to solution of pH as low as 0.9 has a minimal effect on the speed, steerability, or cargo‐transporting capability of micromotors coated with Fe₃O₄ NPs, in stark contrast with those containing Ni segments. Considering the many challenges of biomedical applications, acid‐resistant, magnetically steerable Fe₃O₄‐coated micromotors powered by MHz ultrasound can be a promising prototype for the future development of medical nano‐ and microrobotics.     

Hydrophilic Cu3BiS3 Nanoparticles for Computed Tomography Imaging and Photothermal Therapy

Hydrophilic Cu₃BiS₃ nanoparticles (NPs) have been prepared using the thermal decomposition of precursor complexes in oily‐mixed solvent followed by coating the produced Cu₃BiS₃ NPs with polyvinylpyrrolidone (PVP). The resulting Cu₃BiS₃/PVP NPs remain stable in aqueous solutions over a long period of time, and meanwhile, they show low in vitro cytotoxicity and negligible toxicity to mice in vivo. Cu₃BiS₃/PVP NPs could operate as an efficient dual‐modal contrast agent to simultaneously enhance X‐ray computed tomography imaging and photothermal imaging of tumor model in vivo. Moreover, highly efficient ablation of cancer cells both in vitro and in vivo has been successfully achieved by combining Cu₃BiS₃/PVP NPs with near‐infrared (NIR) laser irradiation. All of the positive results in this study highlight that Cu₃BiS₃/PVP NPs could serve as a promising platform for cancer diagnosis and therapy.     

The upconversion luminescence and magnetism in Yb<Superscript>3+</Superscript>/Ho<Superscript>3+</Superscript> co-doped LaF<Subscript>3</Subscript> nanocrystals for potential bimodal imaging

Biocompatible upconversion nanoparticles with multifunctional properties can serve as potential nanoprobes for multimodal imaging. Herein, we report an upconversion nanocrystal based on lanthanum fluoride which is developed to address the imaging modalities, upconversion luminescence imaging and magnetic resonance imaging (MRI). Lanthanide ions (Yb³⁺ and Ho³⁺) doped LaF₃ nanocrystals (LaF₃ Yb³⁺/Ho³⁺) are fabricated through a rapid microwave-assisted synthesis. The hexagonal phase LaF₃ nanocrystals exhibit nearly spherical morphology with average diameter of 9.8 nm. The inductively coupled plasma mass spectrometry (ICP-MS) analysis estimated the doping concentration of Yb³⁺ and Ho³⁺ as 3.99 and 0.41%, respectively. The nanocrystals show upconversion luminescence when irradiated with near-infrared (NIR) photons of wavelength 980 nm. The emission spectrum consists of bands centred at 542, 645 and 658 nm. The stronger green emission at 542 nm and the weak red emissions at 645 and 658 nm are assigned to ⁵S₂ → ⁵I₈ and ⁵F₅ → ⁵I₈ transitions of Ho³⁺, respectively. The pump power dependence of luminescence intensity confirmed the two-photon upconversion process. The nanocrystals exhibit paramagnetism due to the presence of lanthanide ion dopant Ho³⁺ and the magnetization is 19.81 emu/g at room temperature. The nanocrystals exhibit a longitudinal relaxivity (r ₁) of 0.12 s^?1 mM^?1 and transverse relaxivity (r ₂) of 28.18 s^?1 mM^?1, which makes the system suitable for developing T2 MRI contrast agents based on holmium. The LaF₃ Yb³⁺/Ho³⁺ nanocrystals are surface modified by PEGylation to improve biocompatibility and enhance further functionalisation. The PEGylated nanocrystals are found to be non-toxic up to 50 μg/mL for 48 h of incubation, which is confirmed by the MTT assay as well as morphological studies in HeLa cells. The upconversion luminescence and magnetism together with biocompatibility enables the adaptability of the present system as a nanoprobe for potential bimodal imaging.     

Local structure of polymeric ferrogels

We synthesize hybrid gels incorporating γ‐Fe₂O₃ nanoparticles (NPs), citrate coated, in a polyacrylamide (PAM) network. The local organisation and the rotational degrees of magnetic nanoparticles are probed in the conditions of gel synthesis and also at swelling equilibrium, to correlate the homogeneous/inhomogeneous structure of the ferrogels to the synthesis parameters and to their macroscopic elasticity. NP adsorption on the PAM network at low citrate concentration is responsible for the reinforcing of the polymer structure. At higher citrate concentration, due to a competition between citrate and NPs, the nanoparticles desorb from the polymer structure weakening the system.     

Ex vivo assessment of polyol coated-iron oxide nanoparticles for MRI diagnosis applications: toxicological and MRI contrast enhancement effects

Polyol synthesis is a promising method to obtain directly pharmaceutical grade colloidal dispersion of superparamagnetic iron oxide nanoparticles (SPIONs). Here, we study the biocompatibility and performance as T2-MRI contrast agents (CAs) of high quality magnetic colloidal dispersions (average hydrodynamic aggregate diameter of 16-27 nm) consisting of polyol-synthesized SPIONs (5 nm in mean particle size) coated with triethylene glycol (TEG) chains (TEG-SPIONs), which were subsequently functionalized to carboxyl-terminated meso-2-3-dimercaptosuccinic acid (DMSA) coated-iron oxide nanoparticles (DMSA-SPIONs). Standard MTT assays on HeLa, U87MG, and HepG2 cells revealed that colloidal dispersions of TEG-coated iron oxide nanoparticles did not induce any loss of cell viability after 3 days incubation with dose concentrations below 50 μg Fe/ml. However, after these nanoparticles were functionalized with DMSA molecules, an increase on their cytotoxicity was observed, so that particles bearing free terminal carboxyl groups on their surface were not cytotoxic only at low concentrations (<10 μg Fe/ml). Moreover, cell uptake assays on HeLa and U87MG and hemolysis tests have demonstrated that TEG-SPIONs and DMSA-SPIONs were well internalized by the cells and did not induce any adverse effect on the red blood cells at the tested concentrations. Finally, in vitro relaxivity measurements and post mortem MRI studies in mice indicated that both types of coated-iron oxide nanoparticles produced higher negative T2-MRI contrast enhancement than that measured for a similar commercial T2-MRI CAs consisting in dextran-coated ultra-small iron oxide nanoparticles (Ferumoxtran-10). In conclusion, the above attributes make both types of as synthesized coated-iron oxide nanoparticles, but especially DMSA-SPIONs, promising candidates as T2-MRI CAs for nanoparticle-enhanced MRI diagnosis applications.     

Structural Insight into Stabilization of Pickering Emulsions with Fe3O4@SiO2 Nanoparticles for Enzyme Catalysis in Organic Media

Encapsulation of enzymes with enhanced activity and recyclability in water‐in‐oil Pickering emulsions is a simple and efficient method for their immobilization; however, the effect produced by the structure of colloidal particles on the stabilization of the Pickering emulsion for enzyme catalysis has not been investigated in detail. In this study, four types of hydrophobic Fe₃O₄@SiO₂ nanoparticles (NPs) with similar chemical compositions, particle diameters, but different surface characteristics have been prepared and utilized for enzyme encapsulation in various water‐in‐oil magnetic Pickering emulsions, after which the relationship between NPs structure, size of emulsions droplets, and enzyme activity is examined. The obtained results indicate that (i) the more hydrophobic Fe₃O₄@SiO₂ NPs cause the higher enzyme activity; (ii) the higher hydrophobicity of oil phase also increases the enzyme activity, especially for Fe₃O₄@w‐SiO₂ NPs which form in the solvent of water. The results are mainly attributed to the higher specific surface area of emulsion droplets and interfacial mass transfer of substrates through the interfaces of droplets. The reported data provide new insights into the mechanism of stabilization of Pickering emulsions for enhancing enzyme activity and demonstrate efficient theoretical references for enzyme immobilization and synthesis of stable and active biocatalysts with high recyclability.     

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.     

Magnetic and electromagnetic absorption properties of FeNi alloy nanoparticles supported by reduced graphene oxide

FeNi alloy nanoparticles (NPs) supported by reduced graphene oxide (RGO) (FeNi/RGO nanocomposites) were successfully synthesized through in‐situ reduction. Large amounts of sphere‐like FeNi NPs are uniformly deposited on the RGO nanosheets. The magnetic hysteresis measurement reveals the ferromagnetic behavior of the nanocomposites at room temperature. According to the electromagnetic (EM) characteristics, the FeNi/RGO nanocomposites show outstanding EM absorption properties in the 2–18 GHz range, as evidenced by the wide effective absorption bandwidth (up to 3.3 GHz, with reflection loss R_L < –10 dB) and a minimal R_L (–32 dB) at 12.4 GHz with a thickness of 1.5 mm. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Effect of magnetic field on self-assembling of colloidal Co magnetic nanoparticles

In this paper the formation of 3-D structures composed of Co nanoparticles (NPs) is reported. Structures were obtained by drying a droplet of a colloidal solution of NPs in a magnetic field perpendicular to the substrate. The Co nanoparticles were prepared by thermolysis of Co₂(CO)₈. The 3-D NP structures were characterized by scanning electron microscopy (SEM) and atomic and magnetic force microscopy (AFM/MFM). It has been found that at the border of the droplet, NPs assemble into hexagonally ordered 3-D columns or they form a labyrinthine structure. The formation of the 3-D structures can be explained by the outflow of NPs to the border of the droplet during the drying process. Within this model the pattern formation is dependent on the concentration of the NPs and the degree of alignment of the magnetic moments of NPs in the 3-D columns.     

Responsible nanotechnology development

Chelated gadolinium ions, e.g., Gd-DTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4?C5-nm-sized Gd₂O₃ nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r ₁ and r ₂ values almost as high as those for free Gd³⁺ ions in water. The Gd₂O₃ nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.     

Surface Coating Rescues Proteins from Magnetite Nanoparticle Induced Damage

The presence of magnetic nanoparticles (NPs) in physiological systems induces toxicity through its effects on mitochondrial function and reactive oxygen species (ROS) imbalance. Magnetic NP induced cytotoxicity has been elaborately evaluated for impending threats, however, a detailed investigation is lacking. It is shown that the interaction of Fe₃O₄ NPs with cytochrome c can lead to different events based on the NPs to protein ratio, the solution conditions, and the type of surface protection. At low NPs concentration, rapid binding and subsequent electron transfer are the preferred events while at higher concentration slow oxidative modification of the protein is initiated. The slow event of protein modification yields conformational disorientation, loss of stability, and formation of amyloid‐like structures with cytochrome c. The possibility that the NP induced oxidative stress and age can work in concert to compromise different aspects of cellular quality control processes is discussed. Suitable surface modifications of the NPs inhibit their direct binding to the protein molecules and minimize NP induced toxicity.     

A simplified method for synthesis of Fe3O4@PAA nanoparticles and its application for the removal of basic dyes

A simplified method for synthesis of polyacrylic acid-bound iron oxide magnetic nanoparticles (Fe₃O₄@PAA NPs) was reported. The as-prepared nanoparticles were characterized by TEM, FT-IR, VSM and XRD. Characterization results indicated that PAA was successfully introduced onto the surface of Fe₃O₄ and did not cause any changes in magnetic property. The Fe₃O₄@PAA NPs were used to adsorb rhodamine 6G (R6G) as a model basic dye pollutant from aqueous solution. Kinetics data and adsorption isotherms were better fitted by pseudo-second-order kinetic model and Langmuir isotherm, respectively. The adsorption equilibrium could be reached at about 20 min, showing that the as-prepared adsorbent exhibited extremely rapid adsorption rate. The aqueous solution of the Yellow River was chosen as the test sample, and the results showed that the magnetic adsorbent was efficient for the removal of the basic dye in the real sample.     

Magnetoresistive properties of Fe3O4 nanoparticles embedded in a Cu matrix

We studied ordered arrays of magnetic nanoparticles (NPs) in a nonmagnetic matrix. The influence of annealing temperature and measurement geometry (varying angle between sample surface and external magnetic field direction) on magnetoresistance and coercive field values was established. Measurements were done on the Au(2 nm)/Cu(20 nm)/Fe₃O₄(NPs)/SiO₂/Si system.     

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.     

Synthesis of monodisperse In2O3 nanoparticles and their d0 ferromagnetism

Monodisperse indium oxide (In₂O₃) nanoparticles (NPs) with the average diameter of 11 nm were prepared by a solvothermal method. The In₂O₃ NPs were characterized by X-ray diffraction, Raman and transmission electron microscopy. The intrinsic nature of ferromagnetism in In₂O₃ NPs has been established with the experimental observation of magnetic hysteresis loop. Photoluminescence and UV–visible studies were employed to evidence the presence of oxygen vacancies and revealed that the oxygen vacancies contribute to the ferromagnetism. The origin of ferromagnetism in In₂O₃ NPs may be due to exchange interactions among localized electron spin moments resulting from oxygen vacancies.