Surface Of Magnetic Iron Oxide Nanoparticles Research Articles

Design of doxorubicin encapsulated pH-/thermo-responsive and cationic shell-crosslinked magnetic drug delivery system

The upsurge in cancer cases, such as liver cancer, has claimed millions of lives globally and has prompted the development of novel nanodrug delivery systems. These systems allow cancer drugs to be encapsulated in nanocarriers and delivered to tumor sites, and accordingly, help reduce side effects of the current chemotherapeutic treatments. Herein, we prepared nanocarriers comprising magnetic iron oxide (MIO) nanoparticles that were surface modified with crosslinked Pluronic F127 (PF127) and branched polyethylenimine (bPEI) to form MIOpoly nanocarriers. These nanocarriers were then loaded with doxorubicin (DOX) anticancer drug to form the MIOpoly-DOX complex. The nanocarriers were magnetite and possessed superparamagnetic properties. Small-angle neutron scattering (SANS) analysis indicated that the nanocarriers were thermoresponsive and spherically structured. The characteristic peaks at 1285, 1619, 2844, 2919, 2900, 2840, and 3426 cm−1, corresponding to those of CN, –NH2, –CH2, and OH–, confirmed the successful crosslinking, coating of PF127-bPEI polymers on the surface of MIO nanoparticles and DOX conjugation. The bioavailability of the nanocarriers indicated a more than 85% cell viability when using HepG2 liver cancer cells. A pH (54.8% release in 48 h; pH = 5.4) and temperature (51.0% release in 48 h; 42 °C)-dependent release of DOX was observed, displaying a Korsmeyer–Peppas kinetics model at low pH and Weibull model at high temperatures. The high DOX fluorescence observed for MIOpoly-DOX indicated a high cellular uptake enhanced by alternating magnetic field. These results suggest that MIOpoly synthesized using a combined approach of surface crosslinking and grafted with PF127-bPEI appear to offer promising properties as drug delivery system. Therefore, the nanocarriers developed in the study possess a great potential for targeted delivery and thereby circumventing the limitations of conventional chemotherapy.

Bio-inspired surface modification of iron oxide nanoparticles for active stabilization in hydrogels.

Biological materials employ a variety of dynamic interactions in sophisticated composite structures to function adaptively on different time and length scales. Inspired by such designs we develop a novel surface modification approach to promote dynamic interactions between nanoparticles and polymer chains in physical and double network hydrogels. Physical hydrogels are formed via reversible complexation of borate ions with poly(vinyl alcohol) (PVA) and chemical crosslinks are introduced by electron beam irradiation. Dopamine is used for surface modification of magnetic iron oxide nanoparticles (MNPs) in two different ways: the direct treatment results in anchoring via catechol groups, whereas the indirect method leaves the catechol group on the free surface of MNPs. Although the former particles show very good colloidal stability, they lower the network connectivity, which results in lower plateau modulus, faster terminal relaxation, and lower yield stress, presumably due to imposing an extra distance between PVA chains. In contrast to this passive design, the latter particles actively reinforce the network by forming clusters of physical bonds between catechol groups of the individual particles and the monodiol complexes of the borate ions and PVA chains. Moreover, the additional complexes formed upon the introduction of nanoparticles with active surfaces provide further energy dissipation potential and therefore enhance the toughness. This approach can help develop novel hydrogels with superior toughness and multiple stimuli-responsiveness.

Magnetic Nano-Sized Solid Acid Catalyst Bearing Sulfonic Acid Groups for Biodiesel Synthesis

Abstract In our approach for magnetic iron oxide nanoparticles surface modification, the fabrication of an inorganic shell, consisting of silica by the deposition of preformed colloids onto the nanoparticle surface and functionalization of these particles, was realized. The magnetic nanoparticles, non-coated and coated with silica layer by Stöber method, are functionalized with chlorosulfonic acid. The magnetic nanoparticles (MNPs), in size of 10-13 nm, could be used as acid catalyst in biodiesel production and show superparamagnetic character. The prepared nanoparticles were characterized by different methods including XRD, EDX, FT-IR and VSM. The catalytic activity of the coated and non-coated solid acids was examined in palmitic acid-methanol esterification as an industrial reaction for biodiesel synthesis. Although thin silica layer results in only a minor obstacle with respect to magnetism, it can accelerate the mass transportation due to its relatively porous structure and magnetic core may be more stable in the acidic reaction medium by means of covering process. Accordingly, coating strategy can be efficient way for allowing applications of MNPs in acid catalyzed esterification.

Selective contrast agents with potential to the earlier detection of tumors: Insights on synthetic pathways, physicochemical properties and performance in MRI assays.

Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T2 contrast agent. The T2- weighted images obtained as well as the calculated r2, indicated that MNPs-AA could act as efficient T2 contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the cellular function neither exert cytotoxicity using the three explored doses. The internalization of the nanoparticles on the cellular structure was confirmed quanti and qualitatively using atomic absorption spectroscopy and Prussian blue techniques respectively. From these results, it emerges that ascorbic acid coated-magnetite nanoparticles may be used as alternative contrast agent to avoid or minimize some toxicological issues related to the widely used gadolinium.

A synthetic urinary probe–coated nanoparticles sensitive to fibroblast activation protein α for solid tumor diagnosis

We developed fibroblast activation protein α (FAPα)-sensitive magnetic iron oxide nanoparticles (MNPs) by conjugating a substrate-reporter tandem peptide as a synthetic biomarker to the surface of MNPs (marker-MNPs). In vitro, the marker-MNPs showed stability when treated with serum or urine and exhibited high susceptibility and specificity for FAPα enzyme and 3T3/FAPα cell line. Furthermore, the marker-MNPs were administered to esophageal squamous cell carcinoma xenograft tumor mice; they reached the tumor tissues in the mice, where they were cleaved effectively by the local overexpressed FAPα to release the reporter peptide and filter it into the urine. The tumor targeting and biodistribution of marker-MNPs were verified by in vivo imaging. The cleaved reporter peptides in urine detected by enzyme-linked immunosorbent assay have high diagnostic accuracy for esophageal squamous cell carcinoma (area under the receiver-operating characteristic curve =1.0). Our study implies a promising strategy of utilizing the low-cost and noninvasive synthetic urinary probe–coated nanoparticles for the diagnosis of FAPα-positive solid tumors, except for in renal cancer.

Study on competitive adsorption mechanism among oxyacid-type heavy metals in co-existing system: Removal of aqueous As(V), Cr(III) and As(III) using magnetic iron oxide nanoparticles (MIONPs) as adsorbents

The adsorption and co-adsorption of As(V), Cr(VI) and As(III) onto the magnetic iron oxide nanoparticles (MIONPs) surface were investigated comprehensively to clarify the competitive processes. The results reflected that the MIONPs had remarkable preferential adsorption to As(V) compared with Cr(VI) and As(III). And it was determined, relying on the analysis of heavy metals variations on the MIONPs surface at different co-adsorption stages using FTIR and XPS, that the inner-sphere complexation made vital contribution to the preferential adsorption for As(V), corresponding with the replacement experiments where As(V) could grab extensively active sites on the MIONPs pre-occupied by As(III) or Cr(V) uniaxially. The desorption processes displayed that the strongest affinity between the MIONPs and As(V) where As(III) and Cr(VI) were more inclined to wash out. It is wish to provide a helpful direction with this study for the wastewater treatment involving multiple oxyacid-type heavy metals using MIONPs as adsorbents.

Preparation and characterization of iron oxide (Fe3O4) nanoparticles coated with polyvinylpyrrolidone/polyethylenimine through a facile one-pot deposition route

In this article, we report the electrochemical synthesis and simultaneous in situ coating of magnetic iron oxide nanoparticles (MNPs) with polyvinylpyrrolidone (PVP) and polyethylenimine (PEI). The cathodic deposition was carried out through electro-generation of OH− on the surface of cathode. An aqueous solution of Fe(NO3)3·9H2O (3.4g/L) and FeCl2·4H2O (1.6g/L) was used as the deposition bath. The electrochemical precipitation experiments were performed in the direct current mode under a 10mAcm−2 current density for 30min. Polymer coating was performed in an identical deposition bath containing of 0.5g PVP and 0.5g PEI. The deposited uncoated and PVP-PEI coated MNPs were characterized through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS), vibrating sample magnetometer (VSM), and field-emission scanning and transmission electron microscopies (FE-SEM and TEM). Structural XRD and IR analyses revealed both samples to be composed of pure crystalline magnetite (Fe3O4). Morphological observations through FE-SEM and TEM proved the product to be spherical nanoparticles in the range of 10–15nm. The presence of two coating polymers (i.e. PVP and PEI) on the surface of the electro-synthesized MNPs was proved by FTIR and DLS results. The percentage of the polymer coating (31.8%) on the MNPs surface was also determined based on DSC-TGA data. The high magnetization value, coercivity and remanence values measured by VSM indicated the superparamagnetic nature of both prepared MNPs. The obtained results confirmed that the prepared Fe3O4 nanoparticles had suitable physico-chemical and magnetic properties for biomedical applications.

Preparation of Core-Shell Hybrid Materials by Producing a Protein Corona Around Magnetic Nanoparticles.

Nanoparticles experience increasing interest for a variety of medical and pharmaceutical applications. When exposing nanomaterials, e.g., magnetic iron oxide nanoparticles (MNP), to human blood, a protein corona consisting of various components is formed immediately. The composition of the corona as well as its amount bound to the particle surface is dependent on different factors, e.g., particle size and surface charge. The actual composition of the formed protein corona might be of major importance for cellular uptake of magnetic nanoparticles. The aim of the present study was to analyze the formation of the protein corona during in vitro serum incubation in dependency of incubation time and temperature. For this, MNP with different shells were incubated in fetal calf serum (FCS, serving as protein source) within a water bath for a defined time and at a defined temperature. Before and after incubation the particles were characterized by a variety of methods. It was found that immediately (seconds) after contact of MNP and FCS, a protein corona is formed on the surface of MNP. This formation led to an increase of particle size and a slight agglomeration of the particles, which was relatively constant during the first minutes of incubation. A longer incubation (from hours to days) resulted in a stronger agglomeration of the FCS incubated MNP. Quantitative analysis (gel electrophoresis) of serum-incubated particles revealed a relatively constant amount of bound proteins during the first minutes of serum incubation. After a longer incubation (>20 min), a considerably higher amount of surface proteins was determined for incubation temperatures below 40 °C. For incubation temperatures above 50 °C, the influence of time was less significant which might be attributed to denaturation of proteins during incubation. Overall, analysis of the molecular weight distribution of proteins found in the corona revealed a clear influence of incubation time and temperature on corona composition.

A new procedure for preparation of polyethylene glycol-grafted magnetic iron oxide nanoparticles

Magnetic iron oxide nanoparticles (MNPs) have been widely explored for use in biomedical applications. In the present study, iron oxide nanoparticles were connected to methoxy poly(ethylene glycol) (mPEG) via a new method. The mPEG was acrylated at first and Michael reaction was carried out between acrylated mPEG and 3-aminopropyl triethoxysilane as a coupling agent. The chemical structures of modified mPEG were characterized by Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance. In the next step, iron oxide nanoparticle was coupled with the above-mentioned adduct. Preparation of magnetic nanoparticles with average particle size of 20–30 nm was proved by scanning electron microscopy. The structure of mPEG grafted on the surface of MNPs was confirmed by FT-IR spectroscopy and thermal gravimetric analysis. The synthesized nanoparticles have the potential to be used in different biomedical applications.

Surface functionalization of magnetic nanoparticles formed by self-associating hydrophobized oxidized dextrans

Magnetic iron oxide nanoparticles surface covered with oleic acid layer followed by a second layer of hydrophobized oxidized dextran aldehyde were prepared and tested for physico-chemical properties and ligand- and cell-specific binding. It was demonstrated that oleic acid–iron oxide nanoparticles coated with an additional layer of hydrophobized oxidized dextran were dispersible in buffer solutions and possess surface aldehyde active groups available for further binding of ligands or markers via imine or amine bond formation. Hydrophobized dextrans were synthesized by periodate oxidation and conjugation of various alkanamines to oxidized dextran by imination. Physico-chemical properties, as separation using magnetic field, magnetite concentration, and particle diameter, of the prepared magnetic samples are reported. The biotin-binding protein, neutravidin, was coupled to the particle surface by a simple reductive amination procedure. The particles were used for specific cell separation with high specificity.

One-Step Synthesis of Robust Amine- and Vinyl-Capped Magnetic Iron Oxide Nanoparticles for Polymer Grafting, Dye Adsorption, and Catalysis

Magnetic iron oxide nanoparticles (MIONs) bearing amine and vinyl groups are fabricated straightforwardly using vinyl-based tertiary amine molecules as both alkaline source and ligands based on the coprecipitation of iron ions in aqueous solution. The as-prepared MIONs present amphiphilic performance that can be well-dispersed both in aqueous solution and common organic solvents (e.g., ethanol, dichloromethane and tetrahydrofuran). Transmission electron microscopy (TEM), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM) measurements reveal that the MIONs are superparamagnetic Fe3O4 nanoparticles with a mean diameter below 10 nm. The presence of ligands on the surface of MIONs was confirmed by thermogravimetric analysis (TGA), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS) characterizations. Benefiting from the surface vinyl groups, the MIONs are able to graft polyvinyl-based polymers by in situ polymerization of the corresponding vinyl monomers as confirmed by grafting poly(methyl methacrylate) (PMMA) in this paper. On the basis of their surface amine groups, the MIONs show high adsorption capacity (ca. 0.42 mmol/g) for congo red dye and excellent performance for in situ growth of Pt nanocatalyst. Moreover, the MIONs possess high stability and can be reused several times without obvious decrease of their adsorption capacity and catalytic efficiency. Considering the facile fabrication process and versatile performance of the obtained MIONs, this work may open up new opportunities for the large-scale applications of MIONs.

Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer

Amphiphilic copolymer of folate-conjugated dextran/retinoic acid (FA/DEX-RA) was self-assembled into micelles by direct dissolution method. Magnetic iron oxide nanoparticles (MNPs) coated with oleic acid (OA) were prepared by hydrothermal method and encapsulated within the micelles. Doxorubicin HCl was loaded in the magnetic micelles. The characteristics of the magnetic micelles were determined by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The crystalline state of OA-coated MNPs and their heat capacity were analyzed by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) methods, respectively. The iron content of magnetic micelles was determined using inductively coupled plasma optical emission spectrometry (ICP-OES). Bovine serum albumin (BSA) was used to test the protein binding of magnetic micelles. The cytotoxicity of doxorubicin loaded magnetic micelles was studied on MCF-7 and MDA-MB-468 cells using MTT assay and their quantitative cellular uptake by fluorimetry method. TEM results showed the MNPs in the hydrophobic core of the micelles. TGA results confirmed the presence of OA and FA/DEX-RA copolymer on the surface of MNPs and micelles, respectively. The magnetic micelles showed no significant protein bonding and reduced the IC50 of the drug to about 10 times lower than the free drug.

Stabilization of Magnetic Iron Oxide Nanoparticles in Biological Media by Fetal Bovine Serum (FBS)

A facile method of stabilizing magnetic iron oxide nanoparticles (MNPs) in biological media (RPMI-1640) via surface modification with fetal bovine serum (FBS) is presented herein. Dynamic light scattering (DLS) shows that the size of the MNP aggregates can be maintained at 190 ± 2 nm for up to 16 h in an RPMI 1640 culture medium containing ≥4 vol % FBS. Under transmission electron microscopy (TEM), a layer of protein coating is observed to cover the MNP surface following treatment with FBS. The adsorption of proteins is further confirmed by X-ray photoelectron spectroscopy (XPS). Gel electrophoresis and LC-MS/MS studies reveal that complement factor H, antithrombin, complement factor I, α-1-antiproteinase, and apolipoprotein E are the proteins most strongly attached to the surface of an MNP. These surface-adsorbed proteins serve as a linker that aids the adsorption of other serum proteins, such as albumin, which otherwise adsorb poorly onto MNPs. The size stability of FBS-treated MNPs in biological media is attributed to the secondary adsorbed proteins, and the size stability in biological media can be maintained only when both the surface-adsorbed proteins and the secondary adsorbed proteins are present on the particle's surface.

γ-ray synthesis of composite nanoparticles of noble metals and magnetic iron oxides

Composite nanoparticles composed of noble metal (Au, Pt or Pd) and iron-oxide (Fe 3O 4 or γ-Fe 2O 3) were successfully prepared by γ-ray irradiation of a suspension of iron oxide in an aqueous solution containing noble metal. Formation of the composite nanoparticles was confirmed by the techniques of magnetic separation and XRD. TEM observation revealed that the noble metal nanoparticles were immobilized on the surface of magnetic iron-oxide nanoparticles. Aqueous dispersion of Au/γ-Fe 2O 3 and Au/Fe 3O 4 composite nanoparticles exhibited surface plasmon of Au nanoparticles.