Acid-modified Iron Oxide Nanoparticles Research Articles

Polyacrylic Acid-Modified Superparamagnetic Iron Oxide Nanoparticles Differentiate Between Hyperplastic and Metastatic Breast Cancer Lymph Nodes

The recognition of lymph node (LN) metastasis is critical for breast cancer staging. Axillary lymph node (ALN) puncture or resection followed by biopsy, to determine whether the presence of metastasis is the diagnostic ‘gold standard’ for axillary lymph node metastasis. This procedure is an invasive procedure that triggers a series of complications. To solve this problem, we developed an ultrasmall superparamagnetic polyacrylic acid-modified iron oxide nanoparticles (PAA@IONs), which exhibit excellent physicochemical characteristics and are extremely stable in the aqueous state. They had an average hydrated particle size of 37.81±0.80 nm, average zeta potential of −38.7±3.8 mV, relaxivity R1 of 25.53±1.58 s−1mM−1, and R2 of 43.10±3.43 s−1mM−1. Animal magnetic resonance imaging (MRI) of the inflammatory hyperplasia model and tumor metastasis model of lymph nodes showed that the samples could effectively detect the metastasized tumors in lymph nodes (n =8). The inflammatory lymphadenopathy did not affect lymph node diagnosis, and this property helped overcome the challenge of current lymph node diagnosis, showing high sensitivity (100%) and specificity (83%). Body weight, hematology, coagulation parameters, serum biochemistry, gross anatomy, and histopathological examination of all Sprague-Dawley (SD) rats after intravenous administration of single or multiple doses of PAA@IONs showed no abnormal findings. Therefore, the ultrasmall superparamagnetic iron oxide nanoparticles constructed herein are a promising contrast agent for nodal tumor staging.

Synthesis and Characterization of Citric Acid-Modified Iron Oxide Nanoparticles Prepared with Electrohydraulic Discharge Treatment.

Chemical co-precipitation from ferrous and ferric salts at a 1:1.9 stoichiometric ratio in NH4OH base with ultrasonication (sonolysis) in a low vacuum environment has been used for obtaining colloidal suspensions of Fe3O4 nanoparticles coated with citric acid. Before coating, the nanoparticles were processed by electrohydraulic discharges with a high discharge current (several tens of amperes) in a water medium using a pulsed direct current. Magnetite nanoparticles were obtained with an average crystallite diameter D = 25-28 nm as obtained by XRD and particle sizes of 25 nm as measured by small-angle X-ray scattering. Magnetometry showed that all samples were superparamagnetic. The saturation magnetization for the citric acid covered samples after electrohydraulic processing showed higher value (58 emu/g) than for the directly coated samples (50 emu/g). Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy showed the presence and binding of citric acid to the magnetite surface by chemisorption of carboxylate ions. Hydrodynamic sizes obtained from DLS and zeta potentials were 93 and 115 nm, -26 and -32 mV for the citric acid covered nanoparticles and 226 nm and 21 mV for the bare nanoparticles, respectively. The hydraulic discharge treatment resulted in a higher citric acid coverage and better particle dispersion. The developed method can be used in nanoparticle synthesis for biomedical applications.

A smart magnetic nanosystem for sequential extracellular and intracellular release of proteins for cancer therapy.

Protein therapy, an innovative therapeutic strategy, has been extensively used in the treatment of cancer in recent years. However, the sequential delivery of multiple proteins acting separately intracellular and extracellular to their sites of action remains a challenge. Here, we construct a nanosystem (PEI-PEG-TRAIL@IONP-GOx) to sequentially release tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) extracellularly and glucose oxidase (GOx) intracellularly for synergistic cancer treatment. The nanosystem is built as a core-shell structure. The core is a pH responsive nanoassembly of boronic acid modified iron oxide nanoparticles (FPBA-IONPs) and polyphenol decorated GOx. The shell is a PEGylated polyethyleneimine (PEI-PEG) polymer on which TRAIL was coupled by a matrix metalloproteinase-2 (MMP-2) responsive peptide. Once the nanosystems were magnetically guided to the tumor site, TRAIL was quickly released by the extracellular MMP-2 to induce tumor apoptosis and enhanced the cellular uptake of the cores. After cytosolic delivery, FPBA-IONPs and GOx were disassembled intracellularly to trigger a cascade reaction to generate free radicals for tumor inhibition. Both in vitro and in vivo experiments proved the separate delivery of TRAIL and GOx and their remarkable synergistic anti-cancer effect. We believe that this nanosystem can offer a new approach for the multistage delivery of proteins and accomplish the objective of protein cooperation for cancer treatment.

Stearic Acid Functionalized Iron Nanoparticle Based Magnetic Solid-Phase Extraction (MSPE) for the Determination of Oxadiazon in Purslane by High-Performance Liquid Chromatography (HPLC)

An accurate, simple, and sensitive method was developed for the determination of the herbicide oxadiazon in purslane. The method was based on magnetic solid phase extraction (MSPE) using stearic acid modified iron oxide nanoparticles (Fe3O4@SA) as the adsorbent for preconcentration, followed by the reverse phase high performance liquid chromatography (HPLC) determination of oxadiazon. The MSPE method was optimized using the univariate approach of optimization, where one parameter was tested at different variables and the other parameters were held constant. Using the optimum conditions, the oxadiazon limits of detection and quantification (LOD and LOQ) were 0.29 and 1.0 ng mL−1. The calibration plot of the method was linear across a broad dynamic range from 1.0 to 1000 ng mL−1 with a coefficient of determination equal to 0.9988. The accuracy and applicability of the method was validated by performing spike recovery experiments with purslane samples. The matrix matching calibration strategy was used to mitigate interferences from the sample to attain recovery values between 90 and 110%. The high recoveries and low standard deviations (<10%) verified the accuracy and precision of the developed protocol.

Tannic acid modified iron oxide nanoparticles and its application in protein adsorption: isotherm, kinetic, and thermodynamic study

Iron oxide nanoparticles, such as Fe3O4, are commonly used in various applications, such as drug delivery, magnetic fluid, water purification, and enzyme immobilization. These applications require protein to be adsorbed on the surface of iron oxide nanoparticles. However direct utilization of iron oxide nanoparticles has several drawbacks, thus modification of iron oxide nanoparticles is usually done. In this study, we reported surface modification of Fe3O4 using tannic acid to adsorb bovine serum albumin (BSA). The effect of modification and the BSA adsorption on the Fe3O4 was characterized using Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy, and Transmission Electron Microscopy. Furthermore the adsorption performance of modified and unmodified Fe3O4 was investigated at various initial pH, BSA concentration, and adsorption temperature. Several kinetic and isotherm adsorption models were used to describe the adsorption in this study. It was found that highest BSA adsorption was obtained at pH 4.8, near BSA’s isoelectric point. The adsorption kinetics followed the pseudo 2nd order model and reached equilibrium after 210 min adsorption. Based on Langmuir monolayer adsorption capacity, it was found that tannic acid modified Fe3O4 had 5 times higher adsorption capacity (222 mg/g), compared to unmodified Fe3O4 (46 mg/g). Furthermore, from the thermodynamic study, it was suggested that the BSA adsorption was endothermic, spontaneous, and random in nature.

Dimpled SiO2@γ-Fe2O3 nanocomposites - fabrication and use for arsenic adsorption in aqueous medium.

We report the synthesis of nanocomposites made of silica nanoparticles whose six surface dimples are decorated with magnetic maghemite nanoparticles and their use for detection and recovery of arsenic in aqueous media. Precursor silica nanoparticles have aminated polystyrene chains at the bottom of their dimples and the maghemite nanoparticles are surface functionalized with carboxylic acid groups in two steps: amination with 3-aminopropyltrimethoxysilane, then derivatization with succinic anhydride in the presence of triethylamine. In the end, the colloidal assembly consists of the regioselective grafting of the carboxylic acid-modified iron oxide nanoparticles onto the 6-dimple silica nanoparticles. Several characterization techniques such as transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) are employed to assess the grafting process and study the influence of the maghemite functional groups on the quality of the composites formed. The resulting magnetic nanocomposites are used for the environmentally benign detection and removal of arsenic from aqueous medium, being readily extracted through means of magnetic separation.

Magnetic Quantum Dot Nanobead-Based Fluorescent Immunochromatographic Assay for the Highly Sensitive Detection of Aflatoxin B1 in Dark Soy Sauce.

Herein, we synthesized bifunctional magnetic fluorescent beads (MFBs) with a distinct core/shell structure by encapsulating octadecylamine-coated CdSe/ZnS QDs (OC-QDs) and oleic acid-modified iron oxide nanoparticles (OA-IONPs) into two polymer matrixes with different hydrophobic properties. The OC-QDs and OA-IONPs were mainly distributed in the outer layer of MFBs. The resultant MFBs displayed ca. 226-fold stronger fluorescence emission relative to the corresponding OC-QDs and retained ca. 45.4% of the saturation magnetization of the OA-IONPs. The MFBs were used to purify and enrich aflatoxin B1 (AFB1) from dark soy sauce and then utilized as a fluorescent reporter of immunochromatographic assay (ICA) for the sensitive detection of AFB1. Under the optimal detection conditions, the MFB-based ICA (MFB-ICA) displayed a dynamic linear detection of AFB1 in sauce extract over the range of 5-150 pg/mL with a half maximal inhibitory concentration of 27 ± 3 pg/mL ( n = 3). The detection limits for AFB1 in sauce extract and real dark soy sauce were 3 and 51 pg/mL, respectively, which are considerably better than those of the previously reported fluorescent bead-based ICA methods. The analytical performance of the proposed MFB-ICA in terms of selectivity and accuracy was investigated by analyzing AFB1-spiked dark soy sauce samples. The reliability of the proposed method was further confirmed by ultraperformance liquid chromatography with fluorescence detection. With the combined advantages of QDs and IONPs, the resultant MFBs offer great potential as reporters of ICA for the sensitive detection of trace pollutants in complex matrix samples.

Porous multifunctional fluoropolymer composite foams prepared via humic acid modified Fe3O4 nanoparticles stabilized Pickering high internal phase emulsion using cationic fluorosurfactant as co-stabilizer

Fluoropolymers are very important owing to their excellent application performances, especially in extreme conditions. On the other hand, the preparation of porous fluoropolymers is a difficult task due to unavailability of suitable surfactants as well as tedious synthesis steps. Here we prepared multifunctional porous fluoropolymer composite foams with a simple process of “high internal phase emulsion (HIPE)” by using humic acid modified iron oxide nanoparticles (HA-Fe3O4 NPs) and cationic fluorosurfactant (CFS) (PDMAEMA-b-PHFBA) as co-stabilizer. The inclusion of HA-Fe3O4 NPs in the system made fluoro-HIPE more stable than the emulsion prepared using only CFS or other conventional stabilizers. Morphology of the prepared polyHIPE was easily controlled by altering the concentration of HA-Fe3O4 and/or CFS in the original formulation. Adjustment of the porous structure with open/close cells was performed and the average diameter of the pores tuned between 4.9 and 23 μm. With the increase in specific surface area by using nanoparticles (NPs) and CFS as co-surfactants, Pickering HIPE monoliths adsorbed double amount of oil compared to foams based solely on HIPE template. Multiple functional groups were bound onto Fe3O4 NPs through HA modification that made the fluoro-monolith capable of adsorbing dye, i.e. methylene blue, from water. A simple centrifugation enabled regeneration of the oil soaked foams and adsorption capacity was not decreased after 10 adsorption/regeneration cycles.

Mechanisms of highly stabilized ex-situ oleic acid-modified iron oxide nanoparticles functionalized with 4-pentynoic acid

In this paper, the main objective is to successfully functionalize 4-pentynoic acid on iron oxide nanoparticles (NPs) which arises second objective; to ex-situ modify different concentrations of oleic acid on the NPs. A new understanding has been achieved as to how the concentrations of oleic acid prior ex-situ modification, play a major role in the successful functionalization of 4-pentynoic acid on the NPs. The functionalization proposed is a potential alternative route of creating an acid anhydride from two carboxylic acids without the use of dehydrating agent. Unmodified NPs were synthesized by co-precipitation method and were altered to pH 12 using NH4OH to promote dispersity right before ex-situ modification with oleic acid (0.2–0.8 wt % oleic acid to iron oxide) and subsequent 4-pentynoic acid (1.63 × 10−3 mol) functionalization. Characterizations were conducted by X-ray-diffraction (XRD), Transmission Electron Microscopy (TEM), Thermogravimetric and Differential Thermal analysis (TGA-DTA), Fourier transform infrared spectroscopy (FTIR), proton nucleic magnetic resonance (NMR) and Zetasizer. A monolayer oleic acid is produced for ex-situ modification of 0.2 wt % oleic acid to iron oxide. Whereas the higher concentrations of oleic acid ex-situ modifications generate bilayer oleic acid-modified iron oxide NPs to which, functionalization of 4-pentynoic acid is only successfully performed. The samples pose highly stabilized dispersions at pH 12 varying between -42 and -75 mV, whereas the mean hydrodynamic particle size distributions are achieved at approximately 35–48 nm. Mechanisms of ex-situ modifications of different oleic acid concentrations and functionalization of 4-pentynoic acid on the iron oxide NPs at pH 12 and 333.15 K are also proposed.

Facile Synthesis of Folic Acid-Modified Iron Oxide Nanoparticles for Targeted MR Imaging in Pulmonary Tumor Xenografts.

The purpose of this study was to develop folic acid (FA)-modified iron oxide (Fe3O4) nanoparticles (NPs) for targeted magnetic resonance imaging (MRI) of H460 lung carcinoma cells. Water-dispersible Fe3O4 NPs synthesized via a mild reduction method were conjugated with FA to generate FA-targeted Fe3O4 NPs. The specificity of FA-targeted Fe3O4 NPs to bind FA receptor was investigated in vitro by cellular uptake and cell MRI and in vivo by MRI of H460 tumors. The formed NPs displayed good biocompatibility and ultrahigh r 2 relaxivity (440.01/mM/s). The targeting effect of the NPs to H460 cells was confirmed by in vitro cellular uptake and cell MRI. H460 tumors showed a significant reduction in T2 signal intensity at 0.85h, which then recovered and returned to control at 2.35h. The results indicate that the prepared FA-targeted Fe3O4 NPs have potential to be used as T2 negative contrast agents in targeted MRI.

Theranostic, pH-Responsive, Doxorubicin-Loaded Nanoparticles Inducing Active Targeting and Apoptosis for Advanced Gastric Cancer.

This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(β-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F-P-DOX). Confocal microscopy illustrated that F-P-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F-P-DOX. The better efficacy of F-P-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F-P-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F-P-DOX could be a promising theranostic candidate for AGC treatment.

Miniemulsion-based assembly of iron oxide nanoparticles and synthesis of magnetic polymer nanospheres

A facile method to synthesize core-shell iron oxide/polymer nanospheres has been developed. Oleic acid-modified iron oxide nanoparticles were first prepared by the coprecipitation method. The iron oxide nanoparticles were then assembled into colloidal magnetic nanoparticle clusters (MNCs) by a miniemulsion-based assembly approach. The size of the MNCs can be tuned from about 50 nm to about 93 nm by rationally designing the experimental conditions. Magnetic iron oxide/poly(methyl methacrylate-co-divinylbenzene) (P(MMA-co-DVB)) nanospheres with well-defined core-shell structure and uniform size were finally prepared by seeded emulsion polymerization with the MNCs as the seeds. By the same procedure, core-shell iron oxide/poly(styrene-co-divinylbenzene) (P(St-co-DVB)) nanospheres were also successfully fabricated, demonstrating the versatility of the preparation method. The prepared composite nanospheres have uniform size, high saturation magnetization, and easily functionalized surface, promising for further biomedical applications and liquid phase catalysis.

Influence of Magnetic Nanoparticle Size on the Particle Dispersion and Phase Separation in an ABA Triblock Copolymer

Oleic acid modified iron oxide nanoparticles (IONs) with different sizes were synthesized and mixed with styrene-butadiene-styrene block copolymer (SBS) with a lamellar structure. The octadecene segments on the oleic acid molecules have chemical affinity with the polybutadiene (PB) blocks, which makes IONs tend to be selectively confined in the microphase-separated PB domains. However, the dispersion state strongly depends on the ratio of the particle diameter (d) to the lamellar thickness (l) of the PB domains, which further changes the phase separation of SBS. When d/l ∼0.5, most of IONs are concentrated in the middle of the PB layers at low particle loading. Upon increasing the particle loading, part of IONs contact each other to form long strings due to their strong magnetic interactions. Away from the strings, IONs are either selectively dispersed in the middle and at the interfaces of the PB domains, or randomly distributed at some regions in which the phase separation of SBS is suppressed. The phase separation of SBS transforms from the lamellar structure to a cylinder structure when the IONs loading is higher than 16.7 wt %. As d is comparable to l, IONs aggregate to form clusters of 100 to 300 nm in size, but within the clusters IONs are still selectively dispersed in the PB domains instead of forming macroscopic phase separation. It is interpreted in terms of the relatively small conformational entropy of the middle blocks of SBS; thus, incorporation of nanoparticles does not lead to much loss of conformational entropy. Although incorporation of IONs with d/l ∼1 significantly increases the interfacial curvature and roughness, it has less influence on the phase separation structure of SBS due to the inhomogeneous dispersion. When d is larger than l, IONs are macroscopically separated from the SBS matrix to form clusters of hundreds of nanometers to several micrometers. More interestingly, the phase separation of SBS transforms from the lamellar structure to a two-phase co-continuous structure, probably due to the rearrangement of SBS molecules to cover the clusters with PB segments and the strong magnetic interaction exerting additional force on the SBS matrix during the evaporation of the solvent and the subsequent thermal annealing process.

Macroporous Polymers Obtained in Highly Concentrated Emulsions Stabilized Solely with Magnetic Nanoparticles

Magnetic macroporous polymers have been successfully prepared using Pickering high internal phase ratio emulsions (HIPEs) as templates. To stabilize the HIPEs, two types of oleic acid-modified iron oxide nanoparticles (NPs) were used as emulsifiers. The results revealed that partially hydrophobic NPs could stabilize W/O HIPEs with an internal phase above 90%. Depending upon the oleic acid content, the nanoparticles showed either an arrangement at the oil-water interface or a partial dispersion into the oil phase. Such different abilities to migrate to the interface had significant effects on the maximum internal phase fraction achievable and the droplet size distribution of the emulsions. Highly macroporous composite polymers were obtained by polymerization in the external phase of these emulsions. The density, porosity, pore morphology and magnetic properties were characterized as a function of the oleic acid content, concentration of NPs, and internal phase volume of the initial HIPEs. SEM imaging indicated that a close-cell structure was obtained. Furthermore, the composite materials showed superparamagnetic behavior and a relatively high magnetic moment.

Thiolated polyacrylic acid-modified iron oxide nanoparticles for in vitro labeling and MRI of stem cells

Purpose: The purpose of this study was to develop and characterize new surface-modified iron oxide nanoparticles demonstrating the efficiency to be internalized by human endothelial progenitor cells (EPCs) from umbilical cord blood.Methods: Iron oxide nanoparticles were coated with polyacrylic acid-cysteine (PAA-Cys) by either in situ precipitation or postsynthesis. The nanoparticles were characterized by X-ray powder diffraction. EPCs were labeled with PAA-Cys-modified iron oxide nanoparticles or with uncoated nanoparticles. The relaxivity of uncoated and coated iron oxide nanoparticles as well as EPCs labeled with PAA-Cys-modified iron oxide were determined.Results: Addition of PAA-Cys increased the particle size from 10.4 to 144 and 197 nm, respectively. The X-ray powder diffraction pattern revealed that the particles consist of Fe3O4 with a spinal structure. Postsynthesis coated particles showed a cellular uptake of 85% and 15.26 pg iron/cell. For both types of particles the relaxivity ratio was at least 2-fold higher than that of the gold standard Resovist®.Conclusion: The PAA-Cys coated iron oxide nanoparticles are a promising tool for labeling living cells such as stem cells for diagnostic and therapeutic application in cell-based therapies due to their high relaxivities and their easy uptake by cells.