Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Structure and superparamagnetic behaviour of magnetite nanoparticles in cellulose beads

Superparamagnetic magnetite nanoparticles were obtained starting from a mixture of iron(II) and iron(III) solutions in a preset total iron concentration from 0.04 to 0.8 mol l⁻¹ with ammonia at 25 and 70 °C. The regeneration of cellulose from viscose produces micrometrical spherical cellulose beads in which synthetic magnetite were embedded. The characterization of cellulose-magnetite beads by X-ray diffraction, Scanning and Transmission Electron Microscopy and magnetic measurement is reported. X-ray diffraction patterns indicate that the higher is the total iron concentration and temperature the higher is the crystal size of the magnetite obtained. Transmission Electron Microscopy studies of cellulose-magnetite beads revealed the distribution of magnetite nanoparticles inside pores of hundred nanometers. Magnetite as well as the cellulose-magnetite composites exhibit superparamagnetic characteristics. Field cooling and zero field cooling magnetic susceptibility measurements confirm the superparamagnetic behaviour and the blocking temperature for the magnetite with a mean size of 12.5 nm, which is 200 K.     

Palladium was supported on superparamagnetic nanoparticles: A magnetically recoverable catalyst for Heck reaction

A novel and high-performance palladium-based catalyst for Heck reaction was prepared easily by the co-precipitation method. The catalyst was characterized by transmission electron microscopy (TEM), X-ray powder diffraction (XRD), vibrating sample magnetometry (VSM), X-ray photoelectron spectroscopy (XPS) and atomic absorption spectrophotometry (AAS). The catalyst afforded a fast conversion of the 4-bromonitrobenzene to 4-nitrostilbene at a catalyst loading of 5 mol%, and the efficiency of the catalyst remains unaltered even after 6 repeated cycles. The excellent catalytic performance of the Pd/Fe₃O₄ catalyst might be attributed to the enhanced synergistic effect between Pd nanoparticles and magnetite.     

Investigation on magnetically controlled delivery of doxorubicin from superparamagnetic nanocarriers of gelatin crosslinked with genipin

Gelatin (Type B) nanoparticles were prepared by a single W/O emulsion technique and characterized by infrared (IR) spectra, transmission electron micrographs (TEM), surface potential measurements and magnetization studies. Whereas the IR spectra clearly confirmed the presence of gelatin, genipin and doxorubicin in the loaded nanoparticles, the transmission electron micrographs (TEM) image depicts smooth surface, spherical shape and non-uniform size of nanoparticles (up to 100 nm). The prepared nanoparticles were loaded with doxorubicin, a well known anticancer drug, and in vitro release dynamics of entrapped drug was investigated as a function of various experimental factors such as percent loading of the drug, chemical architecture of the nanocarriers, and pH, temperature, ionic strength and nature of the release medium in presence and absence of magnetic field. The nanoparticles were also studied for their water sorption capacity. The drug release process was analyzed kinetically using Ficks power law and a correlation was established between the quantity of released drug and swelling of the nanoparticles.     

Magnetic force microscopy of superparamagnetic nanoparticles

The use of magnetic force microscopy (MFM) to detect probe-sample interactions from superparamagnetic nanoparticles in vitro in ambient atmospheric conditions is reported here. By using both magnetic and nonmagnetic probes in dynamic lift-mode imaging and by controlling the direction and magnitude of the external magnetic field applied to the samples, it is possible to detect and identify the presence of superparamagnetic nanoparticles. The experimental results shown here are in agreement with the estimated sensitivity of the MFM technique. The potential and challenges for localizing nanoscale magnetic domains in biological samples is discussed.     

Simple synthesis of functionalized superparamagnetic magnetite/silica core/shell nanoparticles and their application as magnetically separable high-performance biocatalysts

Uniformly sized silica-coated magnetic nanoparticles (magnetite@silica) are synthesized in a simple one-pot process using reverse micelles as nanoreactors. The core diameter of the magnetic nanoparticles is easily controlled by adjusting the w value ([polar solvent]/[surfactant]) in the reverse-micelle solution, and the thickness of the silica shell is easily controlled by varying the amount of tetraethyl orthosilicate added after the synthesis of the magnetite cores. Several grams of monodisperse magnetite@silica nanoparticles can be synthesized without going through any size-selection process. When crosslinked enzyme molecules form clusters on the surfaces of the magnetite@silica nanoparticles, the resulting hybrid composites are magnetically separable, highly active, and stable under harsh shaking conditions for more than 15 days. Conversely, covalently attached enzymes on the surface of the magnetite@silica nanoparticles are deactivated under the same conditions.     

Fatigue behaviour of glass fibre reinforced epoxy composites enhanced with nanoparticles

Nanoparticle reinforcement of the matrix in laminates has been recently explored to improve mechanical properties, particularly the interlaminar strength. This study analyses the fatigue behaviour of nanoclay and multiwalled carbon nanotubes enhanced glass/epoxy laminates. The matrix used was the epoxy resin Biresin® CR120, combined with the hardener CH120-3. Multiwalled carbon nanotubes (MWCNTs) 98% and organo-montmorillonite Nanomer I30 E nanoclay were used. Composites plates were manufactured by moulding in vacuum. Fatigue tests were performed under constant amplitude, both under tension–tension and three points bending loadings. The fatigue results show that composites with small amounts of nanoparticles addition into the matrix have bending fatigue strength similar to the obtained for the neat glass fibre reinforced epoxy matrix composite. On the contrary, for higher percentages of nanoclays or carbon nanotubes addition the fatigue strength tend to decrease caused by poor nanoparticles dispersion and formation of agglomerates. Tensile fatigue strength is only marginally affected by the addition of small amount of particles. The fatigue ratio in tension–tension loading increases with the addition of nanoclays and multi-walled carbon nanotubes, suggesting that both nanoparticles can act as barriers to fatigue crack propagation.     

超顺磁性Fe3O4纳米颗粒的制备及修饰

利用2-吡咯烷酮和乙酰丙酮铁为原料制备出Fe3O4磁性纳米粒子,选择偶联剂γ-氨丙基三乙氧基硅烷(NH2C3H6Si(OC2H5)3)对磁性材料进行了表面修饰.经XRD、TEM、VSM、FT-IR测试结果表明,制备出的Fe3O4磁性纳米粒子粒径均一(8～10nm)、结晶度高、磁响应较强;通过控制反应回流时间,可以改变粒子的大小;经表面改性以后,-OH、-NH、-NH2、-C-O、-C-OH等多种功能基团负载到磁性Fe3O4纳米粒子表面,增强了微球的生物相容性.     

超顺磁性Fe3O4纳米颗粒的合成及应用

总结了超顺磁性Fe3O4纳米颗粒的常用制备方法:沉淀法、水热法、微乳液法、模板合成法及生物矿化合成法,并综述了其研究现状,同时比较了它们各自的优缺点及所面临的问题.此外,还概述了超顺磁性Fe3O4纳米颗粒在靶向药物、癌症治疗、磁共振成像(MR I)及生物活性物质的检测和分离等生物医学方面的应用,并对前景进行了展望.     

Low-temperature synthesis of magnetically recoverable,superparamagnetic, photocatalytic,nanocomposite particles

A new, simple, low-temperature method for the synthesis of superparamagnetic, photocatalytic, nanocomposite particles for applications in the decomposition of pollutants in water is presented. The method is based on the coating of clusters of superparamagnetic maghemite (γ-Fe₂O₃) nanoparticles with a photocatalytic anatase layer using the hydrolysis of aqueous TiOSO₄. The clusters of an appropriate size between 100 and 200 nm form by the simultaneous agglomeration of the aminopropyl-triethoxy-silane-grafted maghemite nanoparticles with a size of approximately 15 nm in a suspension of diluted TiOSO₄. During a sudden increase of pH with the addition of NaOH the titania is heterogeneously nucleated at the cluster surfaces. If the hydrolysis was conducted at an elevated temperature of 90 °C, the titania layer was nanocrystalline anatase. The composition of the nanocomposite particles, i.e., the thickness of the anatase layer, can be controlled simply by changing the starting TiOSO₄/Fe₂O₃ ratio for low titania contents, and by multiple coatings to get high titania contents. The photocatalytic activity of the nanocomposites was evaluated in the photocatalytic decomposition of formic acid. The activity seems to increase with an increase in the thickness and the crystallinity of the anatase coating, whereas it decreased after the calcination of the as-synthesized nanocomposite. The coating of the maghemite nanoparticles with a thin layer of insulating silica also slightly improves the photocatalytic activity.     

Nitric oxide donor superparamagnetic iron oxide nanoparticles

This work reports a new strategy for delivering nitric oxide (NO), based on magnetic nanoparticles (MNPs), with great potential for biomedical applications. Water-soluble magnetic nanoparticles were prepared through a co-precipitation method by using ferrous and ferric chlorides in acidic solution, followed by a mercaptosuccinic acid (MSA) coating. The thiolated nanoparticles (SH-NPs) were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). The results showed that the SH-NPs have a mean diameter of 10 nm and display superparamagnetic behavior at room temperature. Free thiol groups on the magnetite surface were nitrosated through the addition of an acidified nitrite solution, yielding nitrosated magnetic nanoparticles (SNO-NPs). The amount of NO covalently bound to the nanoparticles surface was evaluated by chemiluminescense. The SNO-NPs spontaneously released NO in aqueous solution at levels required for biomedical applications. This new magnetic NO-delivery vehicle has a great potential to generate desired amounts of NO directed to the target location.     

Synthesis of superparamagnetic cobalt nanoparticles through solvothermal process

The superparamagnetic (SPM) cobalt nanoparticles with an average size of 2 nm have been prepared through a solvothermal process in the presence of triethanolamine. The synthesized nanoparticles are characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy, and superconducting quantum interference device magnetometer. X-ray diffraction analysis confirms the face centered cubic phase of as-prepared cobalt nanoparticles. Transmission electron microscopy was employed to study the morphology of the as-prepared product, which exhibit spherical-like shape with size around 2 nm. The high resolution transmission electron microscopy image of cobalt nanoparticles shows the lattice spacing value of 0.204 nm. This is well matched with the (111) lattice spacing of fcc Co. XPS revealed the prepared product is pure cobalt. The blocking temperature of 17 K was obtained and confirmed by field-cooled and zero-field-cooled plots. The hysteresis loop revealed the synthesized nanoparticles have SPM character at room temperature.     

Ferrofluids and magnetically guided superparamagnetic particles in flows: a review of simulations and modeling

Ferrofluids are typically suspensions of magnetite nanoparticles, and behave as a homogeneous continuum. The ability of the ferrofluid to respond to an external magnetic field in a controllable manner has made it emerge as a smart material in a variety of applications, such as seals, lubricants, electronics cooling, shock absorbers and adaptive optics. Magnetic nanoparticle suspensions have also gained attraction recently in a range of biomedical applications, such as cell separation, hyperthermia, MRI, drug targeting and cancer diagnosis. In this review, we provide an introduction to mathematical modeling of three problems: motion of superparamagnetic nanoparticles in magnetic drug targeting, the motion of a ferrofluid drop consisting of chemically bound nanoparticles without a carrier fluid, and the breakage of a thin film of a ferrofluid.     

Facile synthesis of superparamagnetic Fe-doped ZnO nanoparticles in liquid polyols

A facile polyol process was established to prepare superparamagnetic Fe-doped ZnO nanoparticles in a liquid polyol using Fe(acac)₃ and Zn(acac)₂ as precursors and triethylene glycol as the solvent. Scanning electron microscopy (SEM) images showed that as-prepared nanoparticles are uniform in size. X-ray diffraction (XRD) analysis revealed that the nanoparticles are of wurtzite structure without an impure phase. The successful doping of the Fe element into the ZnO host was evident by XRD lines shifting and energy dispersive X-ray spectroscopy (EDS) results. Magnetization measurements demonstrated that the Fe-doped ZnO nanoparticles were superparamagnetic at room temperature.     

Enhanced bio-compatibility of ferrofluids of self-assembled superparamagnetic iron oxide-silica core-shell nanoparticles

Self-assembled magnetic colloidal suspensions are sought after by material scientists owing to its huge application potential. The biomedical applications of colloidal nanoparticles necessitate that they are biocompatible, non-interacting, monodispersed and hence the synthesis of such nanostructures has great relevance in the realm of nanoscience. Silica-coated superparamagnetic iron oxide nanoparticles based ferrofluids were prepared using polyethylene glycol as carrier fluid by employing a controlled co-precipitation technique followed by a modified sol-gel synthesis. A plausible mechanism for the formation of stable suspension of SiO2-coated Iron Oxide nanoparticles with a size of about 9 nm dispersed in polyethylene glycol (PEG) is proposed. Core-shell nature of the resultant SiO2-Iron Oxide nanocomposite was verified using transmission electron microscopy. Fourier transform-infrared spectroscopy studies were carried out to understand the structure and nature of chemical bonds. The result suggests that Iron Oxide exist in an isolated state inside silica matrix. Moreover, the presence of silanol bonds establishes the hydrophilic nature of silica shell confirming the formation of stable ferrofluid with PEG as carrier fluid. The magnetic characterization reveals the superparamagnetic behavior of the nanoparticles with a rather narrow distribution of blocking temperatures. These properties are not seen in ferrofluids prepared from Iron Oxide nanoparticles without SiO2 coating. The latter suggests the successful tuning of the inter-particle interactions preventing agglomeration of nanoparticles. Cytotoxicity studies on citric acid coated water based ferrofluid and silica-coated PEG-based ferrofluid were evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium chloride assay and it shows an enhanced compatibility for silica modified nanoparticles.     

DEM analysis of swelling behaviour in granular media

Many granular materials change their volume as they absorb fluids. This phenomenon is called swelling and can be observed in a variety of solids, such as soils, wood, absorbent hygiene products (AHPs) and pharmaceutical excipients. Therefore, an in-depth understanding of grain swelling is of great importance. Since experimental investigations can often provide only limited information, while great insight could be gained from numerical modelling, rigorous numerical models for predicting particle swelling are required. Hence, the objective of this research is to develop and validate a Discrete Element Method (DEM) for swelling of particles. A first order kinetic model was employed to predict the volume expansion of a single grain and subsequently implemented in DEM. The validation of the model was accomplished by comparing the expansion with time of a packed bed made of super absorbent polymer (SAP) particles obtained numerically and experimentally. It was shown that the DEM model can accurately predict the bed expansion. The model was then employed to simulate the swelling of three different materials: superabsorbent polymer (SAP), rice and microcrystalline cellulose (MCC Avicel PH102). As expected, it is demonstrated that the material properties play a significant role on the swelling; the fastest to reach its maximum expansion is the granular bed made of MCC PH102, followed by SAP and rice. However, the highest swelling capacity is achieved with SAP. Moreover, a preliminary DEM analysis of the segregation in a swelling binary mixture is presented in this work. Results suggest that systems which contain a small number of particles, and thus are looser, are more prone to segregation. Future study could advance the developed model to analyse consequences of swelling phenomena in granular materials, such as segregation and heat generation.     

Detection of lysozyme magnetic relaxation switches based on aptamer-functionalized superparamagnetic nanoparticles

Magnetic relaxation switch (MRSw) detection is based on aggregate formation or dissociation when magnetic nanoparticles (MNPs) bind to target molecules. In the aggregated state, the dephasing rate of nearby proton spins is higher than in the dispersed state, resulting in a decrease in the spin-spin relaxation time, T(2). In this work, an MRSw-based nanosensor for lysozyme (Lys) protein detection was achieved using iron oxide nanoparticles conjugated with either Lys aptamer or linker DNA, which can hybridize with the extended part of the aptamer to form clusters. Upon the addition of Lys, the aptamers bind with their targets, leading to disassembly of clusters and an increase in T(2). A detection limit in the nanomolar range was achieved for Lys detection in both buffer and human serum. The determination of Lys level in different types of cancer cell lysates was also performed to demonstrate detection in real clinical samples.     

Novel environmentally friendly synthesis of superparamagnetic magnetite nanoparticles using mechanochemical effect

A novel method for synthesizing superparamagnetic magnetite nanoparticles in water system via coprecipitation under an environmentally friendly condition has been developed. In this method, an almost neutral suspension containing ferrous hydroxide and goethite is used as the starting suspension and subjected to a ball-milling treatment. The product was characterized by transmission electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, dynamic light scattering, superconducting quantum interference device magnetometry, and Mössbauer spectroscopy. The mechanochemical effect generated by the ball-milling treatment promoted the reaction between ferrous hydroxide and goethite even at room temperature, resulting in the formation of homogeneous magnetite nanoparticles. Simultaneously, it also contributed to crystallize the formed magnetite nanoparticles while inhibiting the particle growth. This resulted in the formation of ultrafine magnetite nanoparticles of about 10 nm having a single crystal structure. This method could provide ferromagnetic magnetite nanoparticles with superparamagnetism under the moderate condition without neither heating nor any additives such as surfactant and organic solvent.     

New biomimetic constructs for improved in vivo circulation of superparamagnetic nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIOs) have been produced and used as a potent and versatile contrast media for magnetic resonance imaging (MRI). Despite a number of efforts to improve their surface chemistry and biocompatibility, the SPIOs half life in blood circulation is very short and they are rapidly taken up by the reticuloendothelial system (RES). In this paper we describe a new method that permits to avoid the rapid clearance of SPIOs. Nanoparticles are made biocompatible by encapsulation into autologous red blood cells. These biomimetic constructs preserve the main properties of the cells that escape RES clearance as well as the properties of the nanoparticles that perform even better than in blood suspension with reduced T2*. These SPIO-loaded RBCs are promising intravascular imaging contrast agents and could also be addressed to selected body compartments by an external magnetic field.