PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes

The objective of the present study was to investigate the toxicity of silver nanoparticles (Ag NPs) in vitro. Silver ions (Ag+) have been used in medical treatments for decades whereas Ag NPs have been used in a variety of consumer products within recent years. This study was undertaken to compare the effect of well characterized, PVP-coated Ag NPs (69 nm ± 3 nm) and Ag+ in a human monocytic cell line (THP-1). Characterization of the Ag NPs was conducted in both stock suspension and cell media with or without serum and antibiotics. By using the flowcytometric annexin V/propidium iodide (PI) assay, both Ag NPs and Ag+ were shown to induce apoptosis and necrosis in THP-1 cells depending on dose and exposure time. Furthermore, the presence of apoptosis could be confirmed by the TUNEL method. A number of studies have implicated the production of reactive oxygen species (ROS) in cytotoxicity mediated by NPs. We used the fluorogenic probe, 2′,7′-dichlorofluorescein to assess the levels of intracellular ROS during exposure to Ag NPs and Ag+. A drastic increase in ROS levels could be detected after 6–24 h suggesting that oxidative stress is an important mediator of cytotoxicity caused by Ag NPs and Ag+.     

Biodegradable poly(ɛ-caprolactone)–poly(ethylene glycol) copolymers as drug delivery system

Poly(?-caprolactone)–poly(ethylene glycol) (PCL–PEG) copolymers are important synthetic biomedical materials with amphiphilicity, controlled biodegradability, and great biocompatibility. They have great potential application in the fields of nanotechnology, tissue engineering, pharmaceutics, and medicinal chemistry. This review introduced several aspects of PCL–PEG copolymers, including synthetic chemistry, PCL–PEG micro/nanoparticles, PCL–PEG hydrogels, and physicochemical and toxicological properties.     

Amplified immune response by ginsenoside-based nanoparticles (ginsomes)

We describe here a novel adjuvant of ginsenoside-based nanoparticles (ginsomes) and its activity for up-regulation of immune response in mice. Ginsomes were assembled during removal of the detergent by dialysis in presence of ginseng saponins extracted from the root of Panax ginseng C.A. Meyer, cholesterol and phosphatidyl choline. The nanoparticles were spherical with diameters ranging from 70 to 107 nm, and contained ginsenosides Rb2, Rc, Rb1 and Rd. When co-administered with a model antigen ovalbumin (OVA) in ICR mice, ginsomes at a dose range from 10 to 250 μg promoted significantly higher IgG responses than OVA alone. Co-administration of ginsomes with OVA also significantly increased the levels of specific IgG1, IgG2a, IgG2b and IgG3, as well as T and B lymphocyte proliferation in response to Con A, LPS and OVA than when OVA was used alone. The enhanced IgG titer and subclass levels paralleled the increased production of IFN-γ (Th1 cytokine) and IL-5 (Th2 cytokine). Therefore, ginsomes as an adjuvant have up-regulated both Th1 and Th2 immune responses.     

Preparation and characterization of triclosan nanoparticles intended to be used for the treatment of acne

This work focuses on the preparation and characterization of nanoparticles containing triclosan. Additionally, in vitro percutaneous permeation of triclosan through pig ear skin was performed, and comparisons were made with two commercial formulations: An o/w emulsion and a solution, intended for the treatment of acne. The nanoparticle suspensions were prepared by the emulsification-diffusion by solvent displacement method, using Eudragit® E 100 as polymer. All batches showed a size smaller than 300 nm and a positive Zeta potential, high enough (20-40 mV) to ensure a good physical stability. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) studies suggested that triclosan was molecularly dispersed in the nanoparticle batches containing up to 31% of triclosan, with good encapsulation efficiency (95.9%). The results of the in vitro permeation studies showed the following order for the permeability coefficients: Solution > cream ≈ nanoparticles; while for the amount retained in the skin, the order was as follows: cream > nanoparticles ≈ solution. Nanoparticles, being free of surfactants or other potentially irritant agents, can be a good option for the delivery of triclosan to the skin, representing a good alternative for the treatment of acne.     

纳米石墨碳对人L-02细胞系生长状况的影响

目的研究纳米石墨碳对人正常肝细胞系L-02生长状况的影响。方法电子显微镜观察纳米石墨碳颗粒的形态,激光粒度分析仪测定其粒径及Zeta电位;流式细胞术检测纳米石墨碳作用24 h对L-02肝细胞生长周期的影响;电镜观察细胞剖面,用以考察纳米石墨碳颗粒对L-02肝细胞亚显微结构的影响。结果电镜下纳米石墨碳颗粒呈微小球形,粒径在20～50 nm,表面带负电荷,电位值为-14.8 mV;流式细胞检测结果示实验组L-02肝细胞G0/G1细胞百分数低于对照组,G2/M细胞百分数高于对照组,S期细胞百分数高于对照组;电镜观察纳米石墨碳在细胞质和细胞核内均有分布,实验组肝细胞内的线粒体与对照组无明显差异,胞膜核膜均完整。结论纳米石墨碳颗粒促进了L-02肝细胞的增殖,纳米石墨碳颗粒可以很好地进入到L-02肝细胞内部,未见其对细胞亚显微结构造成损伤。     

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood–brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80^®-coated poly-l-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-l-lactid acid nanoparticles (5 mg/kg), a saline solution of tacrine (5 mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine–lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.     

Oxidative stress and DNA damage responses in rat and mouse lung to inhaled carbon nanoparticles

Abstract

We have investigated whether short-term nose-only inhalation exposure to electric spark discharge-generated carbon nanoparticles (～60 nm) causes oxidative stress and DNA damage responses in the lungs of rats (152 μg/m³; 4 h) and mice (142 μg/m³; 4 h, or three times 4 h). In both species, no pulmonary inflammation and toxicity were detected by bronchoalveolar lavage or mRNA expression analyses. Oxidative DNA damage (measured by fpg-comet assay), was also not increased in mouse whole lung tissue or isolated lung epithelial cells from rat. In addition, the mRNA expressions of the DNA base excision repair genes OGG1, DNA Polβ and XRCC1 were not altered. However, in the lung epithelial cells isolated from the nanoparticle-exposed rats a small but significant increase in APE-1 mRNA expression was measured. Thus, short-term inhalation of carbon nanoparticles under the applied exposure regimen, does not cause oxidative stress and DNA damage in the lungs of healthy mice and rats.     

铈纳米颗粒在辐射领域的研究进展

随着核技术在工业，医学领域等方面应用的迅速发展，人们遭受辐射损伤的可能性也随之增加。辐射损伤防治药物是救治与防护辐射损伤最为有效和直接的手段，但目前的辐射损伤防治药物作用效果有限。铈纳米材料因独特的价态结构，使其具有多种酶学模拟活性和可再生性，体现出优越的抗氧化性，强大的清除自由基功能，可以保护细胞免受辐射损伤，可作为理想的辐射防护剂，并应用于多种生物学领域。对相关文献进行查阅可知，铈纳米颗粒的抗氧化性、高SOD模拟活性、清除自由基能力以及抗辐射能力均源自于Ce³⁺/Ce⁴+相互间的转化、氧空位的形成。本文主要介绍铈纳米颗粒的抗辐射活性基础、辐射防护效应及放疗增敏方面的研究进展，为铈纳米颗粒在辐射方向领域提供理论依据与参考。     

Reactive oxygen species generation by copper(II) oxide nanoparticles determined by DNA damage assays and EPR spectroscopy

Copper(II) oxide nanoparticles (^NPCuO) have many industrial applications, but are highly cytotoxic because they generate reactive oxygen species (ROS). It is unknown whether the damaging ROS are generated primarily from copper leached from the nanoparticles, or whether the nanoparticle surface plays a significant role. To address this question, we separated nanoparticles from the supernatant containing dissolved copper, and measured their ability to damage plasmid DNA with addition of hydrogen peroxide, ascorbate, or both. While DNA damage from the supernatant (measured using an electrophoresis assay) can be explained solely by dissolved copper ions, damage by the nanoparticles in the presence of ascorbate is an order of magnitude higher than can be explained by dissolved copper and must, therefore, depend primarily upon the nanoparticle surface. DNA damage is time-dependent, with shorter incubation times resulting in higher EC₅₀ values. Hydroxyl radical (^?OH) is the main ROS generated by ^NPCuO/hydrogen peroxide as determined by EPR measurements; ^NPCuO/hydrogen peroxide/ascorbate conditions generate ascorbyl, hydroxyl, and superoxide radicals. Thus, ^NPCuO generate ROS through several mechanisms, likely including Fenton-like and Haber-Weiss reactions from the surface or dissolved copper ions. The same radical species were observed when ^NPCuO suspensions were replaced with the supernatant containing leached copper, washed ^NPCuO, or dissolved copper solutions. Overall, ^NPCuO generate significantly more ROS and DNA damage in the presence of ascorbate than can be explained simply from dissolved copper, and the ^NPCuO surface must play a large role.     

二氢卟酚纳米光敏剂对CAL-27细胞的光动力杀伤效应

目的:研究新合成的超支化聚醚酯-二氢卟酚e6纳米光敏剂[hyperbranched poly(ether-ester)-Chlorin e6 nano-photosensitizer,HPEE-ce6]的体外光动力疗法(photodynamic therapy,PDT)对人舌癌CAL-27细胞(human oral tonguecancer CAL-27 cells)的杀伤作用。方法:合成HPEE-ce6后,通过激光共聚焦显微镜观察CAL-27细胞对HPEE-ce6的内摄作用。以游离二氢卟酚e6(Chlorin e6,ce6)为对照组,CAL-27细胞经激光PDT处理(630 nm连续激光照射,功率密度100 mW/cm2、能量密度12 J/cm2、光照600 s),继续孵育细胞24h后,应用MTT法检测HPEE-ce6对CAL-27细胞的光动力杀伤效率。采用SAS 6.12软件包对数据进行统计学处理。结果:HPEE和ce6共价结合,生成直径为50 nm左右的纳米粒子,HPEE-ce6以胞吞方式进入细胞,主要分布于细胞质内。MTT比色法表明,HPEE-ce6对CAL-27细胞的PDT杀伤作用显著强于ce6(P<0.05)。结论:HPEE-ce6对CAL-27细胞具有良好的光动力杀伤作用,且PDT杀伤效率高于ce6。