The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells

Abstract

Introduction: The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species.

Methods: Following an acute whole body inhalation exposure to 500?µg/m³ of nickel nanoparticles for 5?h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure.

Results and conclusions: Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.     

Nanoparticles-containing spray can aerosol: characterization,exposure assessment,and generator design

This is the first report demonstrating that a commercially available household consumer product produces nanoparticles in a respirable range. This report describes a method developed to characterize nanoparticles that were produced under typical exposure conditions when using a consumer spray product. A well-controlled indoor environment was simulated for conducting spray applications approximating a human exposure scenario. Results indicated that, while aerosol droplets were large with a count median diameter of 22 µm during spraying, the final aerosol contained primarily solid TiO₂ particles with a diameter of 75?nm. This size reduction was due to the surface deposition of the droplets and the rapid evaporation of the aerosol propellant. In the breathing zone, the aerosol, containing primarily individual particles (>90%), had a mass concentration of 3.4?mg/m³, or 1.6?×?10⁵ particles/cm³, with a nanoparticle fraction limited to 170 µg/m³, or 1.2?×?10⁵ particles/cm³. The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO₂ per m² alveolar epithelium per minute) and rat (0.03 µg TiO₂) and, consequently, this information was used to design an inhalation exposure system. The system consisted of a computer-controlled solenoid ‘‘finger’’ for generating constant concentrations of spray can aerosols inside a chamber. Test results demonstrated great similarity between the solenoid ‘‘finger’’-dispersed aerosol compared to human-generated aerosol. Future investigations will include an inhalation study to obtain information on dose–response relationships in rats and to use it to establish a No Effect Exposure Level for setting guidelines for this consumer product.     

Ambient Exposure to Criteria Air Pollutants and Risk of Death from Bladder Cancer in Taiwan

To investigate the relationship between air pollution and risk of death from bladder cancer, the authors conducted a matched case-control study using deaths that occurred in Taiwan from 1995 through 2005. Data on all eligible bladder cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of people who died from causes other than cancer or diseases associated with genitourinary problems. The controls were pair matched to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Classification of exposure to municipality air pollution was based on the measured levels of nitrogen dioxide and sulfur dioxide. The results of the present study show that there is a significant positive association between the levels of air pollution and bladder cancer mortality. The adjusted odds ratios (95% confidence interval) were 1.37 (1.03–1.82) for the group with medium air pollution level and 1.98 (1.36–2.88) for the group with high air pollution level when compared to the group with the low air pollution level. Trend analyses showed statistically significant trend in risk of death from bladder cancer with increasing air pollution level. The findings of this study warrant further investigation of the role of air pollutants in the etiology of bladder cancer.     

Oral Insulin Delivery: How Far Are We?

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium.Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized.     

The Surface of Nanoparticle Silicon as Studied by Solid-State NMR

The surface structure and adjacent interior of commercially available silicon nanopowder (np-Si) was studied using multinuclear, solid-state NMR spectroscopy. The results are consistent with an overall picture in which the bulk of the np-Si interior consists of highly ordered (“crystalline”) silicon atoms, each bound tetrahedrally to four other silicon atoms. From a combination of ¹H, ²⁹Si and ²H magic-angle-spinning (MAS) NMR results and quantum mechanical ²⁹Si chemical shift calculations, silicon atoms on the surface of “as-received” np-Si were found to exist in a variety of chemical structures, with apparent populations in the order (a) (Si–O–)₃Si–H > (b) (Si–O–)₃SiOH > (c) (HO–)_nSi(Si)_m(–OSi)_4−m−n ≈ (d) (Si–O–)₂Si(H)OH > (e) (Si–O–)₂Si(–OH)₂ > (f) (Si–O–)₄Si, where Si stands for a surface silicon atom and Si represents another silicon atom that is attached to Si by either a Si–Si bond or a Si–O–Si linkage. The relative populations of each of these structures can be modified by chemical treatment, including with O₂ gas at elevated temperature. A deliberately oxidized sample displays an increased population of (Si–O–)₃Si–H, as well as (Si–O–)₃SiOH sites. Considerable heterogeneity of some surface structures was observed. A combination of ¹H and ²H MAS experiments provide evidence for a substantial population of silanol (Si–OH) moieties, some of which are not readily H-exchangeable, along with the dominant Si–H sites, on the surface of “as-received” np-Si; the silanol moieties are enhanced by deliberate oxidation. An extension of the DEPTH background suppression method is also demonstrated that permits measurement of the T₂ relaxation parameter simultaneously with background suppression.     

磁性纳米粒子在肝细胞癌磁共振成像及靶向治疗方面的研究进展

超顺磁性纳米粒子作为新型材料在临床领域应用广泛,如医学成像及诊断、药物靶向治疗、磁热疗等。它不仅可以在肝细胞癌（HCC）的早期作出特异性诊断,更是一种理想的靶向药物纳米载体。介绍了磁性纳米粒子作为靶向药物载体的性质特点、磁共振成像原理、靶向HCC的作用机制等,重点介绍了磁性纳米粒子的表面修饰及功能化,及其在主动靶向药物输送系统中的应用。认为磁性纳米粒子的应用必将在HCC的诊治中发挥更大的作用。     

伊曲康唑纳米粒的制备及其在小鼠体内的分布

用HPLC法测定了小鼠单剂量(20mg/kg)尾静脉注射伊曲康唑纳米粒及其市售注射剂后心、肝、脾、肺、肾、脑和血浆中的药物浓度.结果表明,伊曲康唑纳米粒在肺中的AUC为注射剂的32.94倍;在心、肾组织的蓄积量减少,在各组织中的半衰期延长,尤以肝、脾、肺为甚.说明伊曲康唑纳米粒的肺靶向性明显优于市售注射剂.     

醋酸地塞米松聚乙二醇化纳米粒的制备及兔体内药动学研究

目的：制备醋酸地塞米松聚乙二醇（PEG）化纳米粒,并测定其在兔体内的药动学参数。方法：以高压均质法制备醋酸地塞米松PEG化纳米粒,用扫描电镜观察纳米颗粒的形态,用激光粒度分析仪测定粒径。建立检测血浆中醋酸地塞米松浓度的HPLC法,以醋酸地塞米松溶液和普通纳米粒作为对照,测定醋酸地塞米松PEG化纳米粒在兔体内的药动学参数。结果：PEG化纳米粒平均粒径为（180±7）nm。体内半衰期为4.79h,AUC0～12为11.81mg.min.L-1,平均滞留时间为3.15h,重要药动学参数比普通纳米粒及溶液剂增加近1倍。结论：醋酸地塞米松PEG化纳米粒可以延长醋酸地塞米松在兔体内的半衰期,达到体内长循环的目的;其表观特征与普通载药纳米粒无明显差异。     

Continuous imaging of plasmon rulers in live cells reveals early-stage caspase-3 activation at the single-molecule level

The use of plasmon coupling in metal nanoparticles has shown great potential for the optical characterization of many biological processes. Recently, we have demonstrated the use of “plasmon rulers” to observe conformational changes of single biomolecules in vitro. Plasmon rulers provide robust signals without photobleaching or blinking. Here, we show the first application of plasmon rulers to in vivo studies to observe very long trajectories of single biomolecules in live cells. We present a unique type of plasmon ruler comprised of peptide-linked gold nanoparticle satellites around a core particle, which was used as a probe to optically follow cell-signaling pathways in vivo at the single-molecule level. These “crown nanoparticle plasmon rulers” allowed us to continuously monitor trajectories of caspase-3 activity in live cells for over 2 h, providing sufficient time to observe early-stage caspase-3 activation, which was not possible by conventional ensemble analyses.     

负载胰岛素壳聚糖接枝醋酸乙烯酯纳米粒的制备和性能

目的:制备负载胰岛素壳聚糖-醋酸乙烯酯共聚物纳米粒并研究其性能。方法:用自由基聚合法合成壳聚糖-醋酸乙烯酯共聚物,该聚合物在水中形成具有疏水核心、亲水表面的纳米粒。采用正交设计试验研究了投料比、引发剂浓度和反应时间对纳米粒粒径的影响。结果:对纳米粒进行了热重分析和红外表征。测定纳米粒的形态、粒径和表面电位(Zeta电位),以胰岛素为模型药物,研究纳米粒的包封和释药性能。结论:纳米粒呈球形,粒径均匀,表面荷正电。胰岛素的包封率可达90%以上。pH6.8的磷酸盐缓冲液中胰岛素释放较慢。结论:该纳米制剂具有较好的物理性能和体外缓释特性。