Weiyue Feng

Comparative study of pulmonary responses to nano- and submicron-sized ferric oxide in rats.

Ferric oxide (Fe(2)O(3)) nanoparticles are of considerable interest for application in nanotechnology related fields. However, as iron being a highly redox-active transition metal, the safety of iron nanomaterials need to be further studied. In this study, the size, dose and time dependent of Fe(2)O(3) nanoparticle on pulmonary and coagulation system have been studied after intratracheal instillation. The Fe(2)O(3) nanoparticles with mean diameters of 22 and 280 nm, respectively, were intratracheally instilled to male Sprague Dawley rats at low (0.8 mg/kgbw) and high (20 mg/kgbw) doses. The toxic effects were monitored in the post-instilled 1, 7 and 30 days. Our results showed that the Fe(2)O(3) nanoparticle exposure could induce oxidative stress in lung. Alveolar macrophage (AM) over-loading of phagocytosed nanoparticle by high dose treatment had occurred, while the non-phagocytosed particles were found entering into alveolar epithelial in day 1 after exposure. Several inflammatory reactions including inflammatory and immune cells increase, clinical pathological changes: follicular hyperplasia, protein effusion, pulmonary capillary vessel hyperaemia and alveolar lipoproteinosis in lung were observed. The sustain burden of particles in AM and epithelium cells has caused lung emphysema and pro-sign of lung fibrosis. At the post-instilled day 30, the typical coagulation parameters, prothrombin time (PT) and activated partial thromboplastin time (APTT) in blood of low dose 22 nm-Fe(2)O(3) treated rats were significantly longer than the controls. We concluded that both of the two-sized Fe(2)O(3) particle intratracheal exposure could induce lung injury. Comparing with the submicron-sized Fe(2)O(3) particle, the nano-sized Fe(2)O(3) particle may increase microvascular permeability and cell lysis in lung epitheliums and disturb blood coagulation parameters significantly.

Particokinetics and Extrapulmonary Translocation of Intratracheally Instilled Ferric Oxide Nanoparticles in Rats and the Potential Health Risk Assessment

Exposure to nanoparticles has presented potential risks to human cardiorespiratory systems. Pulmonary retention and extrapulmonary redistribution of inhaled nanoparticles have been considered to be important contributing factors of cardiorespiratory diseases. In the present work, 22-nm (59)Fe(2)O(3) nanoparticles (radioactive isotope (59)Fe-labeled ferric oxide nanoparticles) were intratracheally instilled into the male Sprague-Dawley rats at a dose of 4 mg/rat. Extrapulmonary distribution of (59)Fe(2)O(3) in organs and its metabolism in lung, blood, urine, and feces were measured for 50 days of exposure. Phagocytosis and clearance of agglomerated nano-Fe(2)O(3) by monocytes/macrophages were observed by histopathology and inductively coupled plasma-mass spectrometry examination. Our results showed intratracheal-instilled nano-(59)Fe(2)O(3) could pass through the alveolar-capillary barrier into systemic circulation within 10 min that consisted with one-compartment kinetic model. The nano-(59)Fe(2)O(3) in the lung was distributed to organs rich in mononuclear phagocytes, including liver, spleen, kidney and testicle. The plasma elimination half-life of nano-(59)Fe(2)O(3) was 22.8 days and the lung clearance rate was 3.06 microg/day, indicating the systemic accumulation and lung retention had occurred. The deposited nano-Fe(2)O(3) in interstitial lung was probably contributed by the particles escaping from alveolar macrophages phagocytosis and macrophages clearance function overloading. Our results suggest that the effect of Fe(2)O(3) nanoparticles exposure, even at low concentration, should be assessed because of the potential lung and systemic cumulative toxicity of the nanoparticles.

Endothelial dysfunction and inflammation induced by iron oxide nanoparticle exposure: Risk factors for early atherosclerosis

More recently, the correlation between exposure to nanoparticles and cardiovascular diseases is of particular concern in nanotoxicology related fields. Nanoparticle-triggered endothelial dysfunction is hypothesized to be a dominant mechanism in the development of the diseases. To test this hypothesis, iron oxide nanoparticles (Fe₂O₃ and Fe₃O₄), as two widely used nanomaterials and the main metallic components in particulate matter, were selected to assess their potential risks on human endothelial system. The direct effects of iron oxide nanoparticles on human aortic endothelial cells (HAECs) and the possible effects mediated by monocyte (U937 cells) phagocytosis and activation were investigated. In the study, HAECs and U937 cells were exposed to 2, 20, 100 μg/mL of 22-nm-Fe₂O₃ and 43-nm-Fe₃O₄ particles. Our results indicate that cytoplasmic vacuolation, mitochondrial swelling and cell death were induced in HAEC. A significant increase in nitric oxide (NO) production was induced which coincided with the elevation of nitric oxide synthase (NOS) activity in HAECs. Adhesion of monocytes to the HAECs was significantly enhanced as a consequence of the up-regulation of intracellular cell adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression, all of which are considered as early steps of atheroscelerosis. Phagocytosis and dissolution of nanoparticles by monocytes were found to simultaneously provoke oxidative stress and mediate severe endothelial toxicity. We conclude that intravascular iron oxide nanoparticles may induce endothelial system inflammation and dysfunction by three ways: (1) nanoparticles may escape from phagocytosis that interact directly with the endothelial monolayer; (2) nanoparticles are phagocytized by monocytes and then dissolved, thus impact the endothelial cells as free iron ions; or (3) nanoparticles are phagocytized by monocytes to provoke oxidative stress responses.

Development of a mild mercaptoethanol extraction method for determination of mercury species in biological samples by HPLC-ICP-MS.

A mild, efficient and convenient extraction method of using 2-mercaptoethanol contained extractant solution combined with an incubator shaker for determination of mercury species in biological samples by HPLC-ICP-MS has been developed. The effects of the concentration of 2-mercaptoethanol, the composition of the extractant solution and the shaking time on the efficiency of mercury extraction were evaluated. The optimization experiments indicated that the quantitative extraction of mercury species from biological samples could be achieved by using 0.1% (v/v) HCl, 0.1% (v/v) 2-mercapoethanol and 0.15% (m/v) KCl extractant solution in an incubator shaker for shaking overnight (about 12h) at room temperature. The established method was validated by analysis of various biological certified reference materials, including NRCC DOLT-3 (dogfish liver), IAEA 436 (tuna fish), IAEA MA-B-3/TM (garfish filet), IAEA MA-M-2/TM (mussel tissue), GBW 08193 (bovine liver) and GBW 08572 (prawn). The analytical results of the reference materials were in good agreement with the certified or reference values of both methyl and total mercury, indicating that no distinguishable transformation between mercury species had occurred during the extraction and determination procedures. The limit of detection (LOD) for methyl (CH(3)Hg(+)) and inorganic mercury (Hg(2+)) by the method are both as 0.2microg L(-1). The relative standard deviation (R.S.D.s) for CH(3)Hg(+) and Hg(2+) are 3.0% and 5.8%, respectively. The advantages of the developed extraction method are that (1) it is easy to operate in HPLC-ICP-MS for mercury species determination since the extracted solution can be directly injected into the HPLC column without pH adjustment and (2) the memory effect of mercury in the ICP-MS measurement system can be reduced.

Icp-ms-based strategies for protein quantification

In the post-genomics era, proteomics has become a central branch in life sciences. An understanding of biological functions will not only rely on protein identification, but also on protein quantification in a living organism. Most of the existing methods for quantitative proteomics are based on isotope labeling combined with molecular mass spectrometry. Recently, a remarkable progress that utilizes inductively coupled plasma-mass spectrometry (ICP-MS) as an attractive complement to electrospray MS and MALDI MS for protein quantification, especially for absolute quantification, has been achieved. This review will selectively discuss the recent advances of ICP-MS-based technique, which will be expected to further mature and to become one of the key methods in quantitative proteomics.

Broad‐Spectrum Antibacterial Activity of Carbon Nanotubes to Human Gut Bacteria

Carbon nanotubes (CNTs) hold promise in manufacturing, environmental, and biomedical applications, as well as food and agricultural industries. Previous observations have shown that CNTs have antimicrobial activity; however, the impact of CNTs to human gut microbes has not been investigated. Here, the antibacterial activity of CNTs against the microbes commonly encountered in the human digestion system--L. acidophilus, B. adolescentis, E. coli, E. faecalis, and S. aureus--are evaluated. The bacteria studied include pathogenic and non-pathogenic, gram-positive and negative, and both sphere and rod strains. In this study, CNTs, including single-walled CNTs (SWCNTs, 1-3 μm), short and long multi-walled CNTs (s-MWCNTs: 0.5-2 μm; l-MWCNTs: >50 μm), and functionalized multi-walled CNTs (hydroxyl- and carboxyl-modification, 0.5-2 μm), all have broad-spectrum antibacterial effects. Notably, CNTs may selectively lyse the walls and membranes of human gut microbes, depending on not only the length and surface functional groups of CNTs, but also the shapes of the bacteria. The mechanism of antibacterial activity is associated with their diameter-dependent piercing and length-dependent wrapping on the lysis of microbial walls and membranes, inducing release of intracellular components DNA and RNA and allowing a loss of bacterial membrane potential, demonstrating complete destruction of bacteria. Thin and rigid SWCNT show more effective wall/membrane piercing on spherical bacteria than MWCNTs. Long MWCNT may wrap around gut bacteria, increasing the area making contact with the bacterial wall. This work suggests that CNTs may be broad-spectrum and efficient antibacterial agents in the gut, and selective application of CNTs could reduce the potential hazard to probiotic bacteria.

Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposure

Microglia as the resident macrophage-like cells in the central nervous system (CNS) play a pivotal role in the innate immune responses of CNS. Understanding the reactions of microglia cells to nanoparticle exposure is important in the exploration of neurobiology of nanoparticles. Here we provide a systemic mapping of microglia and the corresponding pathological changes in olfactory-transport related brain areas of mice with Fe(2)O(3)-nanoparticle intranasal treatment. We showed that intranasal exposure of Fe(2)O(3) nanoparticle could lead to pathological alteration in olfactory bulb, hippocampus and striatum, and caused microglial proliferation, activation and recruitment in these areas, especially in olfactory bulb. Further experiments with BV2 microglial cells showed the exposure to Fe(2)O(3) nanoparticles could induce cells proliferation, phagocytosis and generation of ROS and NO, but did not cause significant release of inflammatory factors, including IL-1β, IL-6 and TNF-α. Our results indicate that microglial activation may act as an alarm and defense system in the processes of the exogenous nanoparticles invading and storage in brain.

Exosomes as Extrapulmonary Signaling Conveyors for Nanoparticle‐Induced Systemic Immune Activation

Evaluation of systemic biosafety of nanomaterials urgently demands a comprehensive understanding of the mechanisms of the undesirable interference and systemic signaling that arises between man-made nanomaterials and biological systems. It is shown that exosomes may act as signal conveyors for nanoparticle-induced systemic immune responses. Exosomes are extracellularly secreted membrane vesicles which act as Trojan horses for the dissemination and intercellular communication of natural nanosized particles (like viruses). Upon exposure to magnetic iron oxide nanoparticles (MIONs), it is possible to dose-dependently generate a significant number of exosomes in the alveolar region of BALB/c mice. These exosomes are quickly eliminated from alveoli into systemic circulation and largely transfer their signals to the immune system. Maturation of dendritic cells and activation of splenic T cells are significantly induced by these exosomes. Furthermore, exosome-induced T-cell activation is more efficient toward sensitized T cells and in ovalbumin (OVA)-sensitized mice than in the unsensitized counterparts. Activation of systemic T cells reveals a T helper 1 polarization and aggravated inflammation, which poses potential hazards to the deterioration of allergic diseases in OVA-sensitized mice. The studies suggest that exosomes may act as conveyors for extrapulmonary signal transduction in nanoparticle-induced immune systemic responses, which are the key in vivo processes of manufactured nanoparticles executing either biomedical functions or toxic responses.

Using ion-pair reversed-phase HPLC ICP-MS to simultaneously determine Cr(III) and Cr(VI) in urine of chromate workers

Urinary chromium speciation analysis can provide available information of the individual exposure levels of Cr(VI) compounds. An analytical method based on ion-pair reversed-phase HPLC combined with ICP-MS to simultaneously determine Cr(III) and Cr(VI) in human urine has been developed for assessing the occupational exposure to chromate. The separation conditions of the method, including the pH value, the concentrations of ion-pair reagent and methanol in the mobile phase were studied. Specially, a high-speed polyetheretherketone (PEEK) column and a typical sample introduction method were employed to avoid the exogenous chromium contamination during the analysis. The separation of Cr(III) and Cr(VI) could be finished within 4min with the detection limits as low as 0.03microgL(-1) at 100microL injections for both of them, providing a convenient method for routine analysis of chromium species. The chromium species in urine of chromate workers were monitored using the developed method. The statistical analysis showed a significant relationship (n=32, p<0.01) between the urinary Cr(VI) and the individual airborne exposure levels, indicating that the urinary Cr(VI) could be used as a convenient and suitable monitor for high level Cr(VI) occupational exposure.

Quantitative imaging of element spatial distribution in the brain section of a mouse model of Alzheimer's disease using synchrotron radiation X-ray fluorescence analysis

A method for quantitative imaging of trace elements in sections of bio-tissues using synchrotron radiation microbeam X-ray fluorescence (SR-μXRF) analysis was developed. The Compton scattering in the SR-μXRF spectrum was utilized as an internal standard to compensate the differences in thickness and density of thin bio-tissue sections. The ratios of element sensitivities to Compton scattering peak obtained from two matrix-matched standard reference materials were used for the calculation of the concentrations of metals in a brain section. The concentrations of Ca, Fe, Cu and Zn in the standard reference material (GBW 08551, pig liver) determined by this method were in good agreement with the certified values. The detection limits of Ca, Fe, Cu and Zn at 2 s detection were 1.15, 0.53, 0.21, and 0.20 μg g−1, respectively. The method has been successfully applied in accurate and precise imaging of the element variations in the brain section of a transgenic mouse model of Alzheimers disease.