Synthesis,characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T ₂ contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T ₂ relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.     

PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

Journal of Nanoparticle Research - Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have...     

Characterization of PEI-coated superparamagnetic iron oxide nanoparticles for transfection: Size distribution,colloidal properties and DNA interaction

Superparamagnetic iron oxide nanoparticles (SPIONs) were coated with polyethylenimine. Here, we briefly describe the synthesis as well as DNA:PEI:SPION complexes and the characterization of the compounds according to their particle size, ζ-potential, morphology, DNA complexing ability, magnetic sedimentation, and colloidal stability. PEI coating of SPIONs led to colloidally stable beads even in high salt concentrations over a wide pH range. DNA plasmids and PCR products encoding for green fluorescent protein were associated with the described beads. The complexes were added to cells and exposed to permanent and pulsating magnetic fields. Presence of these magnetic fields significantly increased the transfection efficiency.     

Toxicity of superparamagnetic iron oxide nanoparticles: Research strategies and implications for nanomedicine

Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.     

Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F₅-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F₅-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.     

Analysis of physicochemical properties of nanoparticles obtained by pulsed electric discharges in water

Aqueous dispersions of nanoparticles are obtained by pulsed electric discharges in water between silver, copper, and iron electrodes. It is shown that depending on the type of the electrode metal, metallic and oxide nanoparticles with the I and II degrees of oxidation, as well as nanoparticles with the magnetite and hematite structure, are formed.     

Pulsed spark-discharge assisted synthesis of colloidal gold nanoparticles in ethanol

A green method, using pulsed spark-discharge (PSD) to synthesize gold nanoparticles (AuNPs) in ethanol, is studied in this article. Unlike conventional methods for metal nanoparticles synthesis, the PSD method does not require the addition of chemical surfactants and stabilizers. The size of PSD–AuNPs is examined by transmission electron microscopy, with a range 5–50 nm. The chemical compounds, crystal structure, and surface plasmon resonance of PSD–AuNPs are studied using energy dispersive X-ray spectroscopy, X-ray diffraction, and UV–Visible spectroscopy, respectively. Zeta potential analysis shows that a negative charge (−40 mV) on the surface of the PSD–AuNPs may be contributing to the stability of the suspension. During the gold electrodes discharge in the ethanol, under an intensive electric field and thermal energy, bulk metallic gold and ethanol may produce AuNPs and varieties of chemical derivatives, which are also studied by GC/MS and FTIR to investigate the suspension mechanism. The analysis results show that there is an oxidation reaction of ethanol occurring during the PSD process to produce ethanol derivatives, such as acetaldehyde, acetic acid, and ethyl acetate, which may modify the surface of AuNPs by coordination of oxygen atoms. However, only acetic acid can form a negative charge by the deprotonation of the carboxylic group of surface in ethanol, resulting in the creation of a repulsion force between the particles to form the stable colloid system. The experimental results indicate that PSD is an alternative green process to synthesize gold nanoparticles suspension in ethanol. Moreover, with a gold rod consumption rate of 15 mg/L, concentrations of gold nanoparticles ~9 ppm have been observed; therefore, the net production rate is around 60%.     

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.     

A Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) study of oleate adsorbed on magnetite nano-particle surface

Magnetite nano-particles were coated with sodium oleate and the spectral behaviour of the coating layer was studied by FTIR spectroscopy after the particles had been heated in air and argon. Magnetite was synthesized by controlled co-precipitation and subsequently coated with sodium oleate. Thermal analysis in combination with mass spectroscopy was carried out to support the FTIR spectroscopic interpretations, but also to monitor the decomposition and surface reaction of oleate adsorbed on the magnetite surface. It was deduced from FTIR and TGA results that the oleate molecules are bonded to iron atoms by a bidentate mononuclear complex and form essentially a single layer with a distance between oleate molecules of ∼36 Å². It was shown by IR as well as Raman spectroscopy that oleic acid, when heated in air, undergoes decomposition implying that new carbon-oxygen bonds are formed. Heating the iron oxide-oleate system in air also implies oxidation of the double bond at the C:9 position of the alkyl chain and formation of intermediate oxygen-rich molecules. An enthalpy change of ΔH = 49.86 J/g was obtained for oleate desorption/decomposition at ∼350 °C under argon atmosphere and a carbonaceous graphitic species resulted from this decomposition.     

Radiation induced synthesis of gold/iron-oxide composite nanoparticles using high-energy electron beam

Composite nanoparticles consisting of gold and iron oxide were synthesized in aqueous solution systems by using a high-energy electron beam. The electron irradiation induces radiation-chemical reaction to form metallic gold nanoparticles. These gold nanoparticles were firmly immobilized on the surface of the support iron oxide nanoparticles. Surface of the support iron oxide nanoparticles are almost fully coated with fine gold nanoparticles. The size of these gold nanoparticles depended on the concentrations of gold ions, polymers and iron oxide nanoparticles in the solutions before the irradiation.     

多孔SiO2包裹磁性纳米颗粒Fe3O4的制备与表征

采用加热分解油酸铁法制备了Fe₃O₄磁性纳米颗粒,并用有机模板和反相微乳液相结合的方法将磁性纳米颗粒包裹在多孔二氧化硅中.用红外光谱(FTIR)研究了不同的处理方式对油酸铁表面官能团的影响及油酸的反应浓度和加热分解油酸铁的过程中升温速率对Fe₃O₄纳米颗粒的影响.结果表明,用乙醇和丙酮处理后的固态蜡状油酸铁表面的油酸基团会受到损害,将不利于加热分解时形成单分散性的Fe₃O₄纳 关键词： 3O₄纳米颗粒')" href="#">Fe₃O₄纳米颗粒 2包裹')" href="#">多孔SiO₂包裹 反相微乳液法 油酸铁     

2-氨基-4-磺酸基-丁酸及其金属离子络合物的光谱研究

本处次对２－氨基－４－磺酸基－丁酸的红外光谱作了初步指认,并早此对其存在形式作出判断、同时,合成了２－氨基－４－磺酸基－丁酸与Ｎａ＾＋、Ｋ＾＋、Ｃａ＾２＋形成的络合物,对其红外光谱及拉曼光谱进行了分析讨论,并对其配位方式进行了比较。结果表明形成络合物后,羟基、磺酸基均参与配位,且破坏了原有分子间的氢键网络,进行了分子间的重新组合。     

Oleic acid coating on the monodisperse magnetite nanoparticles

Monodisperse magnetite nanoparticles provide a more factual model to study the interface interactions between the surfactants and magnetic nanoparticles. Monodisperse magnetite nanoparticles of 7 and 19 nm coated with oleic acid (OA) were prepared by the seed-mediated high temperature thermal decomposition of iron(III) acetylacetonate (Fe(acac)₃) precursor method. Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) reveal that the OA molecules were adsorbed on the magnetic nanoparticles by chemisorption way. Analyses of transmission electron microscopy (TEM) shows the OA provided the particles with better isolation and dispersibility. Thermogravimetric analysis (TGA) measurement results suggest that there were two kinds of different binding energies between the OA molecules and the magnetic nanoparticles. The cover density of OA molecules on the particle surface was significantly various with the size of magnetite nanoparticles. Magnetic measurements of the magnetite nanoparticles show the surface coating reduced the interactions among the nanoparticles.     

Static Magnetic Field Dictates Protein Corona Formation on the Surface of Glutamine‐Modified Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) have become important tools for the imaging and detecting of prevalent diseases for many years. Scientists usually harness their attraction to a static magnetic field (SMF) to increase targeting efficiency and minimize side effects. To prolong blood circulation time and minimize reticuloendothelial system clearance, SPIONs are increasingly designed with a negatively charged surface. Understanding how a SMF affects the SPIONs with a negative surface charge is fundamental to any potential downstream applications of SPIONs as drug delivery carriers and bio‐separation nanoparticles. The goal of our study is to investigate the effect of SMF treatment (204 mT) on the in vitro and in vivo protein corona formed on negatively charged SPIONs. The results reveal that the amount of protein and the composition of protein corona is directly related to the SMF treatment. Compared with the in vivo protein corona, SMF treatment exercises considerable influence on the composition of the in vitro protein corona. The in vitro protein corona formed on SPIONs modulates the secretion of inflammatory cytokines from cells. To the best of our knowledge, this report describes the first demonstration of a SMF as an influencing factor on protein corona formation in vivo. Our results help to elucidate the biological mechanisms of SPIONs with SMF treatment and suggest that the protein corona effect should be considered during the development of a magnetic target.     

The effect of carboxylic acids on the oxidation of coated iron oxide nanoparticles

⁵⁷Fe Mössbauer spectroscopy, XRD, and TEM were used to investigate the effect of mandelic- and salicylic acid coatings on the iron oxide nanoparticles. These two carboxylic acids have similar molecules size and stoichiometry, but different structure and acidity. Significant differences were observed between the Mössbauer spectra of samples coated with mandelic acid and salicylic acid. These results indicate that the occurrence of iron microenvironments in the mandelic- and salicylic acid-coated iron oxide nanoparticles is different. The results can be interpreted in terms of the influence of the acidity of carboxylic acids on the formation, core/shell structure, and oxidation of coated iron oxide nanocomposites.     

Metal-on-oxide nanoparticles produced using laser ablation of microparticle aerosols

A continuous aerosol process has been studied for producing nanoparticles of oxides that were decorated with smaller metallic nanoparticles and are free of organic stabilizers. To produce the oxide carrier nanoparticles, an aerosol of 3–6 μm oxide particles was ablated using a pulsed excimer laser. The resulting oxide nanoparticle aerosol was then mixed with 1.5–2.0 μm metallic particles and this mixed aerosol was exposed to the laser for a second time. The metallic micron-sized particles were ablated during this second exposure, and the resulting nanoparticles deposited on the surface of the oxide nanoparticles producing an aerosol of 10–60 nm oxide nanoparticles that were decorated with smaller 1–5 nm metallic nanoparticles. The metal and oxide nanoparticle sizes were varied by changing the laser fluence and gas type in the aerosol. The flexibility of this approach was demonstrated by producing metal-decorated oxide nanoparticles using two oxides, SiO₂ and TiO₂, and two metals, Au and Ag.     

Synthesis,characterization, conductivity and sensor application study of polypyrrole/silver doped nickel oxide nanocomposites

Conducting polymer composites of polypyrrole (PPy) and silver doped nickel oxide (Ag-NiO) nanocomposites were synthesised by in situ polymerisation of pyrrole with different contents of Ag-NiO nanoparticles. The formation of nanocomposites were studied by Fourier transform infrared (FTIR) and UV–vis spectroscopy, field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and AC and DC conductivity measurements. The sensitivity of ammonia gas through the nanocomposite was analysed with respect to different contents of nanoparticles. Spectroscopic studies showed the shift in the absorption bands of polymer nanocomposite than that of pure PPy indicating the strong interaction between the nanoparticles and polymer chain. FESEM revealed the uniform dispersion of nanoparticles with spherically shaped metal oxide particles in PPy matrix. The XRD pattern indicated a decrease in amorphous domain of PPy with increase in loading of nanoparticles. The higher thermal stability and glass transition temperature of polymer nanocomposites than that of pure PPy were revealed from the TGA and DSC respectively. The dielectric properties, DC and AC conductivity of nanocomposites were much higher than PPy and these electrical properties increases with the loading of nanoparticles. The nanocomposites showed an enhancement in sensitivity towards ammonia gas detection than PPy.     

Synthesis and characterization of silver nanoparticles from (bis)alkylamine silver carboxylate precursors

A comparative study of amine and silver carboxylate adducts [R₁COOAg-2(R₂NH₂)] (R₁ = 1, 7, 11; R₂ = 8, 12) as a key intermediate in NPs synthesis is carried out via differential scanning calorimetry, solid-state FT-infrared spectroscopy, ¹³C CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and various solution NMR spectroscopies (¹H and ¹³C NMR, pulsed field gradient spin-echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination as opposed to bridging bidentate coordination of pure silver carboxylates resulting from the formation of dimeric units. All complexes are packed as lamellar bilayer structures. Silver carboxylate/amine complexes show one first-order melting transition. The evidence presented in this study shows that phase behavior of monovalent metal carboxylates are controlled, mainly, by head group bonding. In solution, insoluble silver salt is stabilized by amine molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate complex as precursor, silver nanoparticles were fabricated. During high-temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce silver nanoparticles of small size. NPs are stabilized by strongly interacting carboxylate and trace amounts of amine derived from the silver precursor interacting with carboxylic acid. A corresponding aliphatic amide obtained from silver precursor at high-temperature reaction conditions is not taking part in the stabilization. Combining NMR techniques with FTIR, it was possible to follow an original stabilization mechanism.

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Graphical abstract The synthesis of a series (bis)alkylamine silver(I) carboxylate complexes in nonpolar solvents were carried out and fully characterized both in the solid and solution. Carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination. The complexes form layered structures which thermally decompose forming nanoparticles stabilized only by aliphatic carboxylates.

     

Fabrication and characterization of iron oxide nanoparticles filled polypyrrole nanocomposites

The effect of iron oxide nanoparticle addition on the physicochemical properties of the polypyrrole (PPy) was investigated. In the presence of iron oxide nanoparticles, PPy was observed in the form of discrete nanoparticles, not the usual network structure. PPy showed crystalline structure in the nanocomposites and pure PPy formed without iron oxide nanoparticles. PPy exhibited amorphous structure and nanoparticles were completely etched away in the nanocomposites formed with mechanical stirring over a 7-h reaction. The thermal stability of the PPy in the nanocomposites was enhanced under the thermo-gravimetric analysis (TGA). The electrical conductivity of the nanocomposites increased greatly upon the initial addition (20 wt%) of iron oxide nanoparticles. However, a higher nanoparticle loading (50 wt%) decreased the conductivity as a result of the dominance of the insulating iron oxide nanoparticles. Standard four-probe measurements indicated a three-dimensional variable-range-hopping conductivity mechanism. The magnetic properties of the fabricated nanocomposites were dependent on the particle loading. Ultrasonic stirring was observed to have a favorable effect on the protection of iron oxide nanoparticles from dissolution in acid. A tight polymer structure surrounds the magnetic nanoparticles, as compared to a complete loss of the magnetic iron oxide nanoparticles during conventional mechanical stirring for the micron-sized iron oxide particles filled PPy composite fabrication.     

Applications of polymeric micelles with tumor targeted in chemotherapy

The chitosan-coated magnetic nanoparticles (CS MNPs) were in situ synthesized by cross-linking method. In this method; during the adsorption of cationic chitosan molecules onto the surface of anionic magnetic nanoparticles (MNPs) with electrostatic interactions, tripolyphosphate (TPP) is added for ionic cross-linking of the chitosan molecules with each other. The characterization of synthesized nanoparticles was performed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS/ESCA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and vibrating sample magnetometry (VSM) analyses. The XRD and XPS analyses proved that the synthesized iron oxide was magnetite (Fe₃O₄). The layer of chitosan on the magnetite surface was confirmed by FTIR. TEM results demonstrated a spherical morphology. In the synthesis, at higher NH₄OH concentrations, smaller sized nanoparticles were obtained. The average diameters were generally between 2 and 8?nm for CS MNPs in TEM and between 58 and 103?nm in DLS. The average diameters of bare MNPs were found as around 18?nm both in TEM and DLS. TGA results indicated that the chitosan content of CS MNPs were between 15 and 23?% by weight. Bare and CS MNPs were superparamagnetic. These nanoparticles were found non-cytotoxic on cancer cell lines (SiHa, HeLa). The synthesized MNPs have many potential applications in biomedicine including targeted drug delivery, magnetic resonance imaging?(MRI), and magnetic hyperthermia.