纳米氧化铁的制备及其掺杂效应

纳米氧化铁作为气敏材料得到广泛重视。本文重点介绍了近年来应用比较普遍的合成纳米氧化铁的方法,如:溶胶—凝胶法、共沉淀法、水热法、水解法,并指出了各种方法的优缺点;同时,介绍了在掺杂了不同的物质后纳米氧化铁具有的独特的气敏性能;最后,对氧化铁基气敏元件的烧成工艺进行了比较。     

Oleic Acid Protects Endothelial Cells from Silica-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs)-Induced Oxidative Stress and Cell Death

Superparamagnetic iron oxide nanoparticles (SPIONs) have great potential for use in medicine, but they may cause side effects due to oxidative stress. In our study, we investigated the effects of silica-coated SPIONs on endothelial cells and whether oleic acid (OA) can protect the cells from their harmful effects. We used viability assays, flow cytometry, infrared spectroscopy, fluorescence microscopy, and transmission electron microscopy. Our results show that silica-coated SPIONs are internalized by endothelial cells, where they increase the amount of reactive oxygen species (ROS) and cause cell death. Exposure to silica-coated SPIONs induced accumulation of lipid droplets (LD) that was not dependent on diacylglycerol acyltransferase (DGAT)-mediated LD biogenesis, suggesting that silica-coated SPIONs suppress LD degradation. Addition of exogenous OA promoted LD biogenesis and reduced SPION-dependent increases in oxidative stress and cell death. However, exogenous OA protected cells from SPION-induced cell damage even in the presence of DGAT inhibitors, implying that LDs are not required for the protective effect of exogenous OA. The molecular phenotype of the cells determined by Fourier transform infrared spectroscopy confirmed the destructive effect of silica-coated SPIONs and the ameliorative role of OA in the case of oxidative stress. Thus, exogenous OA protects endothelial cells from SPION-induced oxidative stress and cell death independent of its incorporation into triglycerides.     

氧化铁磁性纳米粒子的表面修饰及应用

氧化铁磁性纳米粒子因其优异的性能,广泛应用于环境分离、生物活性物质的富集和分离等领域,近年来引起了广泛的关注和研究。文章总结了氧化铁肱性纳米粒子表面修饰方法及相关应用,并对其前号进行了展望。     

Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity

Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR) (CD-1) mice were exposed to a single, low (10 mg/kg) or high (100 mg/kg) dose of positively-charged polyethyleneimine-Fe₂O₃-NPs (PEI-NPs), or negatively-charged poly(acrylic acid)-Fe₂O₃-NPs (PAA-NPs) during critical windows of organogenesis (gestation day (GD) 8, 9, or 10). A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges) and testes (positive only) of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42%) and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero). Alternatively, negatively-charged PAA-NPs induced fetal loss (22%) earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term.     

In Vitro/In Vivo Toxicity Evaluation and Quantification of Iron Oxide Nanoparticles

Increasing biomedical applications of iron oxide nanoparticles (IONPs) in academic and commercial settings have alarmed the scientific community about the safety and assessment of toxicity profiles of IONPs. The great amount of diversity found in the cytotoxic measurements of IONPs points toward the necessity of careful characterization and quantification of IONPs. The present document discusses the major developments related to in vitro and in vivo toxicity assessment of IONPs and its relationship with the physicochemical parameters of IONPs. Major discussion is included on the current spectrophotometric and imaging based techniques used for quantifying, and studying the clearance and biodistribution of IONPs. Several invasive and non-invasive quantification techniques along with the pitfalls are discussed in detail. Finally, critical guidelines are provided to optimize the design of IONPs to minimize the toxicity.     

Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.     

Synergistic Effect of Repolarization of M2 to M1 Macrophages Induced by Iron Oxide Nanoparticles Combined with Lactate Oxidase

Metabolic reprogramming of tumors with the accompanying reprogramming of glucose metabolism and production of lactate accumulation is required for the subsequent development of tumors. Recent evidence has indicated that tumor-secreted lactate can promote an oncolytic immune microenvironment within the tumor. Furthermore, tumor-secreted lactate directly induces polarization of tumor-supportive M2 macrophages. However, oxidized tumor-secreted lactate in the tumor microenvironment can be exploited. Iron oxide nanoparticles have shown promising anticancer potential by activating tumor-suppressing macrophages. Furthermore, lactate oxidase (LOX) generally oxidizes tumor-secreted lactate and subsequently converts to pyruvate. Particularly, the ratio of M2 macrophages to M1 macrophages corresponds with tumor growth. In this study, we present iron oxide nanoparticles with carboxylic acid combined with LOX that enhance antitumor efficacy as a synergistic effect on the repolarization of tumor-supportive M2 macrophages to tumor-suppressive M1 macrophages in a tumor microenvironment. After M2 macrophages treated with iron oxide nanoparticles were combined with LOX, the ratio of M1 macrophages was significantly greater than iron oxide nanoparticles alone or with LOX alone. It is concluded that the inhibition of cancer cell proliferation by ratio of M1 macrophages was observed. This study suggests that the iron oxide nanoparticles combined with LOX could be potentially used for potentiating immune checkpoint inhibitor therapies for cancer treatment.     

Marine Collagen-Based Antibacterial Film Reinforced with Graphene and Iron Oxide Nanoparticles

It has become more widely available to use biopolymer-based films as alternatives to conventional plastic-based films due to their non-toxic properties, flexibility, and affordability. However, they are limited in application due to deficiencies in their properties. The marine collagen was the specimen for the present study. Thus, the main objective was to reinforce marine collagen-based films with 1.0% (w/w of the dry polymer weight) of iron oxide nanoparticles (IO-NPs), graphene oxide nanoparticles (GO-NPs), or a combination of both oxides (GO-NPs/IO-NPs) as antibacterial and antioxidant additives to overcome some of the limitations of the film. In this way, the nanoparticles were incorporated into the film-forming solution (2% w/v in acetic acid, 0.05 M) and processed by casting. Thereafter, the films were dried and analyzed for their physicochemical, mechanical, microstructural, and functional properties. The results show that the effective combination of GO-NPs/IO-NPs enhanced the physicochemical properties by increasing the water contact angle (WCA) of the films from 77.2 to 84.4° and their transparency (T) from 0.5 to 5.2. Furthermore, these nanoparticles added antioxidant and antibacterial value to the films, with free radical inhibition of up to 95.8% and 23.8 mm of bacteria growth inhibition (diameter). As a result, both types of nanoparticles are proposed as suitable additives to be incorporated into films and enhance their different properties.     

Development and Screening of a Series of Antibody‐Conjugated and Silica‐Coated Iron Oxide Nanoparticles for Targeting the Prostate‐Specific Membrane Antigen

The prostate‐specific membrane antigen (PSMA) is an established target for the delivery of cancer therapeutic and imaging agents due to its high expression on the surface of prostate cancer cells and within the neovasculature of other solid tumors. Here, we describe the synthesis and screening of antibody‐conjugated silica‐coated iron oxide nanoparticles for PSMA‐specific cell targeting. The humanized anti‐PSMA antibody, HuJ591, was conjugated to a series of nanoparticles with varying densities of polyethylene glycol and primary amine groups. Customized assays utilizing iron spectral absorbance and enzyme‐linked immunoassay (ELISA) were developed to screen microgram quantities of nanoparticle formulations for immunoreactivity and cell targeting ability. Antibody and PSMA‐specific targeting of the optimized nanoparticle was evaluated using an isogenic PSMA‐positive and PSMA‐negative cell line pair. Specific nanoparticle targeting was confirmed by iron quantification with inductively coupled plasma mass spectrometry (ICP‐MS). These methods and nanoparticles support the promise of targeted theranostic agents for future treatment of prostate and other cancers.     

Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma

The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.     

Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging

Superparamagnetic iron-oxide particles (SPIO) are used in different ways as contrast agents for magnetic resonance imaging (MRI): Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite), different coatings (none, dextran, carboxydextran, polystyrene) and different hydrodynamic diameters (20–850 nm) for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC), which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe₃O₄ particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.     

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3–24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.     

Bi-Functional Silica Nanoparticles Doped with Iron Oxide and CdTe Prepared by a Facile Method

Cadmium telluride (CdTe) and iron oxide nanoparticles doped silica nanospheres were prepared by a multistep method. Iron oxide nanoparticles were first coated with silica and then modified with amino group. Thereafter, CdTe nanoparticles were assembled on the particle surfaces by their strong interaction with amino group. Finally, an outer silica shell was deposited. The final products were characterized by X-ray powder diffraction, transmission electron microscopy, vibration sample magnetometer, photoluminescence spectra, Fourier transform infrared spectra (FT-IR), and fluorescent microscopy. The characterization results showed that the final nanomaterial possessed a saturation magnetization of about 5.8 emu g⁻¹ and an emission peak at 588 nm when the excitation wavelength fixed at 380 nm.     

Biohybrid Nanostructured Iron Oxide Nanoparticles and Satureja hortensis to Prevent Fungal Biofilm Development

Cutaneous wounds are often superinfected during the healing process and this leads to prolonged convalescence and discomfort. Usage of suitable wound dressings is very important for an appropriate wound care leading to a correct healing. The aim of this study was to demonstrate the influence of a nano-coated wound dressing (WD) on Candida albicans colonization rate and biofilm formation. The modified WD was achieved by submerging the dressing pieces into a nanofluid composed of functionalized magnetite nanoparticles and Satureja hortensis (SO) essential oil (EO). Chemical composition of the EO was established by GC-MS. The fabricated nanostructure was characterized by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Differential Thermal Analysis (DTA) and Fourier Transform-Infrared Spectroscopy (FT-IR). The analysis of the colonized surfaces using (Scanning Electron Microscopy) SEM revealed that C. albicans adherence and subsequent biofilm development are strongly inhibited on the surface of wound dressing fibers coated with the obtained nanofluid, comparing with regular uncoated materials. The results were also confirmed by the assay of the viable fungal cells embedded in the biofilm. Our data demonstrate that the obtained phytonanocoating improve the resistance of wound dressing surface to C. albicans colonization, which is often an etiological cause of local infections, impairing the appropriate wound healing.     

Magnetic Hyperthermia Nanoarchitectonics via Iron Oxide Nanoparticles Stabilised by Oleic Acid: Anti-Tumour Efficiency and Safety Evaluation in Animals with Transplanted Carcinoma

In this study, we developed iron oxide nanoparticles stabilised with oleic acid/sodium oleate that could exert therapeutic effects for curing tumours via magnetic hyperthermia. A suspension of iron oxide nanoparticles was produced and characterised. The toxicity of the synthesised composition was examined in vivo and found to be negligible. Histological examination showed a low local irritant effect and no effect on the morphology of the internal organs. The efficiency of magnetic hyperthermia for the treatment of transplanted Walker 256 carcinoma was evaluated. The tumour was infiltrated with the synthesised particles and then treated with an alternating magnetic field. The survival rate was 85% in the studied therapy group of seven animals, while in the control group (without treatment), all animals died. The physicochemical and pharmaceutical properties of the synthesised fluid and the therapeutic results, as seen in the in vivo experiments, provide insights into therapeutic hyperthermia using injected magnetite nanoparticles.     

Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.     

Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles

Copper oxide nanoparticles (CuO NPs) were intratracheally instilled into lungs at concentrations of 0, 0.15, and 1.5 mg/kg bodyweight to 7-week-old Sprague–Dawley rats. The cytotoxicity, immunotoxicity, and oxidative stress were evaluated, followed by proteomic analysis of bronchoalveolar lavage fluid (BALF) and lungs of rats. The CuO NPs-exposed groups revealed dose-dependent increases in total cells, polymorphonuclear leukocytes, lactate dyhydrogenase, and total protein levels in BALF. Inflammatory cytokines, including macrophage inflammatory protein-2 and tumor necrosis factor-α, were increased in the CuO NPs-treated groups. The expression levels of catalase, glutathione peroxidase-1, and peroxiredoxin-2 were downregulated, whereas that of superoxide dismutase-2 was upregulated in the CuO NPs-exposed groups. Five heat shock proteins were downregulated in rats exposed to high concentrations of CuO NPs. In proteomic analysis, 17 proteins were upregulated or downregulated, and 6 proteins were validated via Western blot analysis. Significant upregulation of 3-hydroxy-3-methylglutaryl-CoA synthase and fidgetin-like 1 and downregulation of annexin II, HSP 47 and proteasome α1 occurred in the CuO NPs exposed groups. Taken together, this study provides additional insight into pulmonary cytotoxicity and immunotoxicity as well as oxidative stress in rats exposed to CuO NPs. Proteomic analysis revealed potential toxicological biomarkers of CuO NPs, which also reveals the toxicity mechanisms of CuO NPs.