Cellular level loading and heating of superparamagnetic iron oxide nanoparticles

Superparamagnetic iron oxide nanoparticles (NPs) hold promise for a variety of biomedical applications due to their properties of visualization using magnetic resonance imaging (MRI), heating with radio frequency (rf), and movement in an external magnetic field. In this study, the cellular loading (uptake) mechanism of dextran- and surfactant-coated iron oxide NPs by malignant prostate tumor cells (LNCaP-Pro5) has been studied, and the feasibility of traditional rf treatment and a new laser heating method was evaluated. The kinetics of cell loading was quantified using magnetophoresis and a colorimetric assay. The results showed that loading of surfactant-coated iron oxide NPs with LNCaP-Pro5 was saturable with time (at 24 h) and extracellular concentration (11 pg Fe/cell at 0.5 mg Fe/mL), indicating that the particles are taken up by an "adsorptive endocytosis" pathway. Dextran-coated NPs, however, were taken up less efficiently (1 pg Fe/cell at 0.5 mg Fe/mL). Loading did not saturate with concentration suggesting uptake by fluid-phase endocytosis. Magnetophoresis suggests that NP-loaded cells can be held using external magnetic fields in microcirculatory flow velocities in vivo or in an appropriately designed extracorporeal circuit. Loaded cells were heated using traditional rf (260A, 357 kHz) and a new laser method (532 nm, 7 ns pulse duration, 0.03 J/pulse, 20 pulse/s). Iron oxide in water was found to absorb sufficiently strongly at 532 nm such that heating of individual NPs and thus loaded cells (1 pg Fe/cell) was effective (<10% cell survival) after 30 s of laser exposure. Radio frequency treatment required higher loading (>10 pg Fe/cell) and longer duration (30 min) when compared to laser to accomplish cell destruction (50% viability at 10 pg Fe/cell). Scaling calculations show that the pulsed laser method can lead to single-cell (loaded with NPs) treatments (200 degrees C temperature change at the surface of an individual NP) unlike traditional rf heating methods which can be used only for bulk tissue level treatments. In a mixture of normal and NP-loaded malignant tumor cells, the malignant cells were selectively destroyed after laser exposure leaving the unloaded normal cells intact. These studies hold promise for applications in cell purification and sorting and extracorporeal blood treatments in vitro.     

Simultaneous thermomagnetic and dilatometric measurements in a study of the Fe2O3 metastable transformation

Simultaneous measurements of variations in magnetic and dilatometric properties were successfully used to detect the phase transition occurring during the thermal treatment of iron(III) oxide microcrystals. The increase of the compacting pressure, i.e. the increase of the interparticular number, favours the irreversibleγ→α transition. An unusual phase of iron(III) oxide, different from theγ-phase, has been unambiguously demonstrated. Its stability seems to be improved by the surface energy excess due to the highly-divided state.     

A novel and reusable magnetic nanocatalyst developed based on graphene oxide incorporated strontium nanoparticles for the facial synthesis of β‐enamino ketones under solvent‐free conditions

A novel magnetic SrFeGO nanocatalyst (NC) was synthesized through a simple sol–gel technique by introducing strontium and iron oxide nanoparticles onto graphene. The synthesized NC was characterized using FT‐IR and FE‐SEM. Subsequently, the catalytic activity of SrFeGO was tested in a reaction between β‐dicarbonyl compounds and aniline derivatives to gain β‐enamino ketone derivatives under solvent‐free conditions. It was found that SrFeGO NC is a potential catalyst for the synthesis of β‐enamino ketones. The β‐enamino ketone produced by such reactions could be isolated in high purity without the need for chromatographic purifications. The newly prepared magnetic graphene oxide nanocomposite could be recovered and reused for numerous times with no significant decrease in efficiency. Moreover, the protocol has the advantages of excellent yielding (up to 98%) in short a reaction time, benefitting an easy workup procedure and being environmentally friendly.     

Green biosynthesis,characterization, and cytotoxic effect of magnetic iron nanoparticles using Brassica Oleracea var capitata sub var rubra (red cabbage) aqueous peel extract

The green method of nanoparticle synthesis, which is an environment and living-friendly method, is an updated subject that has appeared as an alternative to conventional methods such as physical and chemical synthesis. In this presented study, the green synthesis of magnetic iron oxide nanoparticles (IONPs) from iron (III) chloride by using Brassica oleracea var. capitata sub.var. rubra aqueous peel extract has been reported. The prepared IONPs were characterized with fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-VIS), zeta potential, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The cytotoxic effects of IONPs on MCF-7 breast cancer cell line were studied by MTT assay, and migrative effect of its were carried out by the wound healing assay. It was found that the mean particle size of IONPs was 675 ± 25 nm, and the polydispersity index was 0.265 PDI. It was also determined that these nanoparticles had an anti-proliferative impact on the MCF-7 breast cancer cell line depending on the dosage. Characterization results support the successful synthesis of nanoparticles, and the dose-dependent cytotoxic effects of nanoparticles on MCF-7 cells also make it a potential chemotherapeutic agent for breast cancer treatment.     

Biogenous iron oxide-immobilized palladium catalyst for the solvent-free Suzuki–Miyaura coupling reaction

Iron oxide produced by iron-oxidizing bacteria, Leptothrix ochracea, (biogenous iron oxide: BIO) was used as a support for immobilized palladium catalysts with organic cross-linkers. Palladium immobilized on BIO bearing imidazolium chloride delivered the desired biaryl products in sufficient yields in the Suzuki–Miyaura coupling reactions under solvent-free conditions and could be reused several times without significant loss of catalytic activity. It is shown that BIO can be exploited as a useful support for immobilization of palladium and the BIO-immobilized palladium catalyst effectively promotes the solvent-free Suzuki–Miyaura coupling reactions.     

In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals

The unique properties of magnetic nanocrystals provide them with high potential as key probes and vectors in the next generation of biomedical applications. Although superparamagnetic iron oxide nanocrystals have been extensively studied as excellent magnetic resonance imaging (MRI) probes for various cell trafficking, gene expression, and cancer diagnosis, further development of in vivo MRI applications has been very limited. Here, we describe in vivo diagnosis of cancer, utilizing a well-defined magnetic nanocrystal probe system with multiple capabilities, such as small size, strong magnetism, high biocompatibility, and the possession of active functionality for desired receptors. Our magnetic nanocrystals are conjugated to a cancer-targeting antibody, Herceptin, and subsequent utilization of these conjugates as MRI probes has been successfully demonstrated for the monitoring of in vivo selective targeting events of human cancer cells implanted in live mice. Further conjugation of these nanocrystal probes with fluorescent dye-labeled antibodies enables both in vitro and ex vivo optical detection of cancer as well as in vivo MRI, which are potentially applicable for an advanced multimodal detection system. Our study finds that high performance in vivo MR diagnosis of cancer is achievable by utilizing improved and multifunctional material properties of iron oxide nanocrystal probes.     

Iron Oxide Nanoparticles Embedded onto 3D Mesochannels of KIT‐6 with Different Pore Diameters and Their Excellent Magnetic Properties

Here, we report the results of our detailed study on the fabrication of iron oxide magnetic nanoparticles confined in mesoporous silica KIT‐6 with a 3D structure and large, tunable pore diameters. It was confirmed by XRD, nitrogen adsorption, high‐resolution (HR) TEM, and magnetic measurements that highly dispersed iron oxide nanoparticles are occupied inside the mesochannels of KIT‐6. We also demonstrated that the size of the iron oxide nanoparticle can be controlled by simply changing the pore diameter of the KIT‐6 and the weight percentage of the iron oxide nanoparticles. The effect of the weight percentage and size of the iron oxide nanoparticles, and the textural parameters of the support on the magnetic properties of iron oxide/KIT‐6 has been demonstrated. The magnetization increases with decreasing iron content in the pore channels of KIT‐6, whereas coercivity decreases for the same samples. Among the KIT‐6 materials studied, KIT‐6 with 7.5 wt % of iron showed the highest saturation magnetic moment and magnetic remanence. However, all the samples register a coercivity of around 2000 Oe, which is generally observed for the hard magnetic materials. In addition, we have found a paramagnetic‐to‐superparamagnetic transition at low temperature for samples with different iron content at low temperature. The cause for this exciting transition is also discussed in detail. Magnetic properties of the iron oxide loaded KIT‐6 were also compared with pure iron oxide and iron oxide loaded over SBA‐15. It was found that iron oxide loaded KIT‐6 showed the highest magnetization due to its 3D structure and large pore volume. The pore diameter of the iron oxide loaded KIT‐6 support also plays a critical role in controlling the magnetization and the blocking temperature, which has a direct relation to the particle diameter and increases from 48 to 63 K with an increase in the pore diameter of the support from 8 to 11.3 nm.     

One-pot synthesis and characterization of size-controlled bimagnetic FePt-iron oxide heterodimer nanocrystals

A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined.     

Interfacing living yeast cells with graphene oxide nanosheaths

The first example of the encapsulation of living yeast cells with multilayers of GO nanosheets via LbL self-assembly is reported. The GO nanosheets with opposite charges are alternatively coated onto the individual yeast cells while preserving the viability of the yeast cells, thus affording a means of interfacing graphene with living yeast cells. This approach is expanded by integrating other organic polymers or inorganic nanoparticles to the cells by hybridizing the entries with GO nanosheets through LbL self-assembly. It is demonstrated that incorporated iron oxide nanoparticles can deliver magnetic properties to the biological systems, allowing the integration of new physical and chemical functions for living cells with a combination of GO nanosheets.     

Effect of pH, ionic strength, foreign ions and temperatures on the sorption of Eu(III) on attapulgite-iron oxide magnetic composites

In this paper, the attapulgite-iron oxide magnetic composites were synthesized by coprecipitation method and were characterized by SEM, XRD and FTIR in detail. The characterization results indicated that the iron oxide was successfully formed on the surface of attapulgite. The prepared attapulgite-iron oxide magnetic composites were applied as adsorbents to remove Eu(III) from aqueous solutions by using batch sorption experiments under different experimental conditions. The sorption properties of Eu(III) on bare attapulgite were also performed as comparison. The results indicated that the sorption of Eu(III) on attapulgite-iron oxide magnetic composites was strongly dependent on pH and temperature. The attapulgite-iron oxide magnetic composites can be separated from aqueous solutions using magnetic separation method in large scale. At low pH values, the sorption of Eu(III) was influenced by ionic strength and pH obviously, while the sorption of Eu(III) was not affected by ionic strength at high pH values. The sorption of Eu(III) was dominated by ion exchange or outer-sphere surface complexation at low pH values, and mainly by inner-sphere surface complexation at high pH values. The thermodynamic parameters (i.e., ?G ^°, ?S ^°, ?H ^°) calculated from the temperature dependent sorption isotherms indicated that the sorption of Eu(III) on attapulgite-iron oxide magnetic composites was an endothermic and spontaneous process. Although the sorption capacities of Eu(III) on attapulgite-iron oxide magnetic composites were a little lower than those of Eu(III) on bare attapulgite, the magnetic separation in large scale is suitable for the application of the magnetic composites in the preconcentration of Eu(III) from large volumes of aqueous solutions in possible real applications.     

Inductive heating with magnetic materials inside flow reactors

Superparamagnetic nanoparticles coated with silica gel or alternatively steel beads are new fixed-bed materials for flow reactors that efficiently heat reaction mixtures in an inductive field under flow conditions. The scope and limitations of these novel heating materials are investigated in comparison with conventional and microwave heating. The results suggest that inductive heating can be compared to microwave heating with respect to rate acceleration. It is also demonstrated that a very large diversity of different reactions can be performed under flow conditions by using inductively heated flow reactors. These include transfer hydrogenations, heterocyclic condensations, pericyclic reactions, organometallic reactions, multicomponent reactions, reductive cyclizations, homogeneous and heterogeneous transition-metal catalysis. Silica-coated iron oxide nanoparticles are stable under many chemical conditions and the silica shell could be utilized for further functionalization with Pd nanoparticles, rendering catalytically active heatable iron oxide particles.     

Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling

High-quality biocompatible magnetic iron oxide (Fe3O4) nanocrystals were developed through a ligand exchange process of hydrophobically capped nanocrystals with hydrophilic molecules. By simple modulation of the nanocrystal surface ligand charge properties, we have been able to prepare magnetic nanocrystals with excellent intracellular labeling capabilities that efficiently label a variety of cell types without the need for additional transport facilitating agents. The excellent intracellular labeling capability of the newly developed cationic WSIO has further led to successful MRI monitoring of the migration of neural stem cells in rat spinal cord. The magnetic nanocrystals developed here have great potential in applications for labeling of various cell types and also the monitoring of cell-based medical treatments and cancer metastasis.     

原位沉析法制备磁性氧化铁羟基磷灰石/壳聚糖棒材

首先通过化学沉淀法制备磁性氧化铁羟基磷灰石(Fe3O4/HA),然后以壳聚糖(CS)为基体,利用原位沉析法将Fe3O4/HA与CS复合,制得磁性Fe3O4/HA/CS复合材料.经XRD、粒径分布和PPMS测试,结果表明了Fe3O4/HA复合物的生成.系统研究了磁性Fe3O4/HA/CS棒材力学性能的影响因素,最终确定Fe3O4与HA质量比为3∶17,磁性Fe3O4/HA与CS质量比为9∶91时,棒材的力学性能最优,弯曲强度可达到87.0 MPa,弯曲模量1.57 GPa.     

Synthesis of aligned hematite nanoparticles on chitosan–alginate films

Iron oxide nanoparticles are being viewed with interest owing to the great potential they have in the biomedical applications like MRI contrast enhancement, targeted drug delivery, hyperthermia and recently in magnetic separation of cancer cells from the body. Templated synthesis has been considered ideal for synthesis of iron oxide nanoparticles as particles are attracted magnetically, in addition to usual flocculation through van der Waals attraction. Biological templates are attractive owing to their biocompatibility and the attractive porosity and surface chemistry that nature provides. Polysaccharides like chitosan and alginate have been employed in the synthesis of a polyion complex, which provided the active-binding sites for iron(II) ions in solution to bind. The natural organization of chitosan and alginate into a porous film has been exploited to synthesize spherical iron oxide nanoparticles through careful calcination of the iron(II) conjugate film. Our experiments indicate that the formed nanoparticles are highly crystalline, confirm to the hematite structure and have a superparamagnetic response with a low coercivity of 116 Oe. Particles thus synthesized were highly monodisperse with hydrodynamic diameter of 1.8 nm. The symmetric porosity of the film translates into the synthesis of well-aligned nanoparticles of iron oxide. Compared to synthesis in solution, the film-assisted synthesis offered a greater degree of control over the particle size distribution pattern, with the chitosan–alginate template providing the needed spatial separation to prevent the aggregation due to magnetostatic coupling. Such hematite nanoparticles can either be used directly or converted to paramagnetic magnetite by reduction. Zeta potential measurements indicate highly stable nanoparticles, which can therefore be conjugated to cationic liposomes carrying drugs and magnetically guided to target sites.     

Occurrence and prevention of photodissolution at the phase junction of magnetite and titanium dioxide

A stable magnetic photocatalyst was prepared by coating a magnetic core with a layer of photoactive titanium dioxide. A direct deposition of titanium dioxide onto the surface of magnetic iron oxide particles proved ineffective in producing a stable magnetic photocatalyst, with high levels of photodissolution being observed with these samples. This observed photodissolution is believed to be due to the dissolution of the iron oxide phase, induced by the photoactive the titanium dioxide layer due to electronic interactions at the phase junction in these magnetic photocatalysts. The introduction of an intermediate passive SiO₂ layer between the titanium dioxide phase and the iron oxide phase inhibited the direct electrical contact and hence prevented the photodissolution of the iron oxide phase. The magnetic photocatalyst is for use in slurry-type reactors from which the catalyst can be easily recovered by the application of an external magnetic field.     

Design of water-based ferrofluids as contrast agents for magnetic resonance imaging

We report the synthesis, characterization and relaxometric study of ferrofluids based on iron oxide, with potential for use as magnetic resonance imaging (MRI) contrast agents (CAs). The effect of different cost-effective, water-based surface modification approaches which can be easily scaled-up for the large scale synthesis of the ferrofluids has been investigated. Surface modification was achieved by silanization, and/or coating with non-toxic commercial dispersants (a lauric polysorbate and a block copolymer with pigment affinic groups, namely Tween 20 and Disperbyk 190) which were added after or during iron oxide nanoparticle synthesis. It was observed that all the materials synthesized functioned as negative contrast agents at physiological temperature and at frequencies covered by clinical imagers. The relaxometric properties of the magnetic nanoparticles were significantly improved after surface coating with stabilizers compared to the original iron oxide nanoparticles, with particular reference to the silica-coated magnetic nanoparticles. The results indicate that the optimization of the preparation of colloidal magnetic ferrofluids by surface modification is effective in the design of novel contrast agents for MRI by enabling better or more effective interaction between the coated iron oxide nanoparticles and protons present in their aqueous environment.     

G-quadruplex DNA and ligand interaction in living cells using NMR spectroscopy

Gathering structural information from biologically relevant molecules inside living cells has always been a challenging task. In this work, we have used multidimensional NMR spectroscopy to probe DNA G-quadruplexes inside living Xenopus laevis oocytes. Some of these structures can be found in key regions of chromosomes. G-quadruplexes are considered potential anticancer therapeutic targets and several lines of evidence indirectly point out roles in key biological processes, such as cell proliferation, genomic instability or replication initiation. However, direct demonstrations of the existence of G-quadruplexes in vivo are scarce. Using SOFAST-HMQC type spectra, we probed a tetramolecular G-quadruplex model made of d(TG₄T)₄ inside living Xenopus laevis oocytes. Our observations lead us to conclude that the quadruplex structure is formed within the cell and that the intracellular environment preferentially selects a conformation that most resembles the one found in vitro under KCl conditions. We also show for the first time that specific ligands targeting G-quadruplexes can be studied using high resolution NMR directly inside living cells, opening new avenues to study ligand binding discrimination under physiologically relevant conditions with atomic detail.     

Facile synthesis of magnetic silica-mannan nanocomposites for enhancement in internalization and immune response of dendritic cells

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively exploited in biomedicine, especially as contrasting agents. In this work, SPIONs are of our interest as directing agents to the targeted dendritic cells (DCs). Mannan extracted from Saccharomyces cerevisiae was used as DCs targeting moieties. Herein, nanocomposites of silica magnetic nanoparticle-mannan (S-SPION-MN) were successfully synthesized as a magnetically assisted delivery system. The materials before Silica magnetic nanoparticles (S-SPION) and after mannan modification were characterized using a vibrating sample magnetometer to confirm their superparamagnetic character. The change in zeta potential from highly negative charge to slightly negative charge of the composites suggested the successful attachment of mannan on their surface. Chemical analysis using x-ray photoelectron spectroscopy revealed the attachment of mannan through chemical bonding, corresponding to the observation of high stability of the particles over a two-week period. The synthesized materials were investigated for cytotoxicity, DC maturation, cytokine production, and cellular uptake. Moderate cell viability was observed after stimulating cells with the particulate mannan, S-SPION-MN, due to high activation of DCs. Under a magnetic induction, S-SPION-MN showed significant enhancement of DCs targeting within 15 min. Owing to the incorporation of mannan and SPIONs, the S-SPION-MN greatly enhanced cellular uptake and accordingly resulted in high DC activation and maturation. The resulted nanocomposites can be beneficial as a potential candidate in antigen delivery to targeted immune cells for further in vivo study.     

Fluorine insertion reactions into pre-formed metal oxides

Fluorine insertion reactions have been shown to be capable of modifying the physical properties of metal oxide materials, as a result of the structural and electronic consequences of fluorine insertion. This has been applied to copper oxide systems and has led to an enhanced understanding of the requirements for superconductivity, and more recently to other magnetic metal oxide systems where it has been shown to tune the magnetic properties of these materials. This review focuses on some important aspects of research on low temperature fluorine insertion reactions into pre-formed metal oxides, since 1998, and reports some new results.     

氧化铁磁性纳米粒子固定化酶*

纳米粒子作为酶固定化的载体,当其具有磁性时,制备的固定化酶易于从反应体系中分离和回收,操作简便;并且利用外部磁场可以控制磁性材料固定化酶的运动方式和方向,替代传统的机械搅拌方式,提高固定化酶的催化效率。在众多纳米材料中,氧化铁因其在磁性、催化等多方面的良好特性而倍受瞩目。本文对近年来各种氧化铁磁性纳米粒子固定化酶,尤其是固定化脂肪酶和蛋白酶的制备方法及其应用做了较为详细的阐述,对这些氧化铁磁性纳米粒子固定化酶的优缺点和发展前景进行了讨论。