Cellular senescence as a response to multiwalled carbon nanotube (MWCNT) exposure in human mesothelial cells.

Cellular senescence is a stable cell cycle arrest induced by diverse triggers, including replicative exhaustion, DNA damaging agents, oncogene activation, oxidative stress, and chromatin disruption. With important roles in aging and tumor suppression, cellular senescence has been implicated also in tumor promotion. Here we show that certain multiwalled carbon nanotubes (MWCNTs), as fiber-like nanomaterials, can trigger cellular senescence in primary human mesothelial cells. Using in vitro approaches, we found manifestation of several markers of cellular senescence, especially after exposure to a long and straight MWCNT. These included inhibition of cell division, senescence-associated heterochromatin foci, senescence-associated distension of satellites, LMNB1 depletion, γH2A.X nuclear panstaining, and enlarged cells exhibiting senescence-associated ß-galactosidase activity. Furthermore, genome-wide transcriptome analysis revealed many differentially expressed genes, among which were genes encoding for a senescence-associated secretory phenotype. Our results clearly demonstrate the potential of long and straight MWCNTs to induce premature cellular senescence. This finding may find relevance in risk assessment of workplace safety, and in evaluating MWCNT's use in medicine such as drug carrier, due to exposure effects that might prompt onset of age-related diseases, or even carcinogenesis.

Systematic Investigations of Annealing and Functionalization of Carbon Nanotube Yarns.

Carbon nanotube yarns (CNY) are a novel carbonaceous material and have received a great deal of interest since the beginning of the 21st century. CNY are of particular interest due to their useful heat conducting, electrical conducting, and mechanical properties. The electrical conductivity of carbon nanotube yarns can also be influenced by functionalization and annealing. A systematical study of this post synthetic treatment will assist in understanding what factors influences the conductivity of these materials. In this investigation, it is shown that the electrical conductivity can be increased by a factor of 2 and 5.5 through functionalization with acids and high temperature annealing respectively. The scale of the enhancement is dependent on the reducing of intertube space in case of functionalization. For annealing, not only is the highly graphitic structure of the carbon nanotubes (CNT) important, but it is also shown to influence the residual amorphous carbon in the structure. The promising results of this study can help to utilize CNY as a replacement for common materials in the field of electrical wiring.

The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats.

BACKGROUND: Biological effects of tailor-made multi-walled carbon nanotubes (MWCNTs) without functionalization were investigated in vivo in a two-year carcinogenicity study. In the past, intraperitoneal carcinogenicity studies in rats using biopersistent granular dusts had always been negative, whereas a number of such studies with different asbestos fibers had shown tumor induction. The aim of this study was to identify possible carcinogenic effects of MWCNTs. We compared induced tumors with asbestos-induced mesotheliomas and evaluated their relevance for humans by immunohistochemical methods. METHODS: A total of 500 male Wistar rats (50 per group) were treated once by intraperitoneal injection with 109 or 5 × 109 WHO carbon nanotubes of one of four different MWCNTs suspended in artificial lung medium, which was also used as negative control. Amosite asbestos (108 WHO fibers) served as positive control. Morbid rats were sacrificed and necropsy comprising all organs was performed. Histopathological classification of tumors and, additionally, immunohistochemistry were conducted for podoplanin, pan-cytokeratin, and vimentin to compare induced tumors with malignant mesotheliomas occurring in humans. RESULTS: Treatments induced tumors in all dose groups, but incidences and times to tumor differed between groups. Most tumors were histologically and immunohistochemically classified as malignant mesotheliomas, revealing a predominantly superficial spread on the serosal surface of the abdominal cavity. Furthermore, most tumors showed invasion of peritoneal organs, especially the diaphragm. All tested MWCNT types caused mesotheliomas. We observed highest frequencies and earliest appearances after treatment with the rather straight MWCNT types A and B. In the MWCNT C groups, first appearances of morbid mesothelioma-bearing rats were only slightly later. Later during the two-year study, we found mesotheliomas also in rats treated with MWCNT D - the most curved type of nanotubes. Malignant mesotheliomas induced by intraperitoneal injection of different MWCNTs and of asbestos were histopathologically and immunohistochemically similar, also compared with mesotheliomas in man, suggesting similar pathogenesis. CONCLUSION: We showed a carcinogenic effect for all tested MWCNTs. Besides aspect ratio, curvature seems to be an important parameter influencing the carcinogenicity of MWCNTs.

Surface properties of CNTs and their interaction with silica.

In order to improve the embedding of carbon nanotubes (CNTs) in cement-based matrices, silica was deposited on the sidewall of CNTs by a sol-gel method. Knowledge of the conditions of CNTs' surfaces is a key issue in understanding the corresponding interaction mechanisms. In this study various types of CNTs synthesized using acetonitrile, cyclohexane, and methane were investigated with regard to their physicochemical surface properties. Significant differences in surface polarity as well as in the wetting properties of the CNTs, depending on the precursors used, were revealed by combining electro-kinetic potential and contact angle measurements. The hydrophobicity of CNTs decreases by utilising the carbon sources in the following order: cyclohexane, methane, and finally acetonitrile. The XPS analysis, applied to estimate the chemical composition at the CNT surface, showed nitrogen atoms incorporated into the tube structure by using acetonitrile as a carbon source. It was found that the simultaneous presence of nitrogen- and/or oxygen-containing sites with different acid-base properties increased the surface polarity of the CNTs, imparting amphoteric characteristics to them and improving their wetting behaviour. Regarding the silica deposition, strong differences in adsorption capacity of the CNTs were observed. The mechanism of silica adsorption through interfacial bond formation was discussed.

Antioxidant multi-walled carbon nanotubes by free radical grafting of gallic acid: new materials for biomedical applications.

OBJECTIVES: To prove the possibility of covalently functionalizing multi-walled carbon nanotubes (CNTs) by free radical grafting of gallic acid on their surface with the subsequent synthesis of materials with improved biological properties evaluated by specific in-vitro assays. METHODS: Antioxidant CNTs were synthesized by radical grafting of gallic acid onto pristine CNTs. The synthesis of carbon nanotubes was carried out in a fixed-bed reactor and, after the removal of the amorphous carbon, the grafting process was performed. The obtained materials were characterized by fluorescence and Fourier transform infrared spectroscopy (FT-IR) analyses. After assessment of the biocompatibility and determination of the disposable phenolic group content, the antioxidant properties were evaluated in terms of total antioxidant activity and scavenger ability against 2,2'-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl and peroxyl radicals. Finally the inhibition activity on acetylcholinesterase was evaluated. KEY FINDINGS: The covalent functionalization of CNTs with gallic acid was confirmed and the amount of gallic acid bound per g of CNTs was found to be 2.1±0.2 mg. Good antioxidant and scavenging properties were recorded in the functionalized CNTs, which were found to be able to inhibit the acetylcholinesterase with potential improved activity for biomedical and pharmaceutical applications. CONCLUSIONS: For the first time, a free radical grafting procedure was proposed as a synthetic approach for the covalent functionalization of CNTs with an antioxidant polyphenol.

Carbon Nanotubes Filled with Ferromagnetic Materials.

Carbon nanotubes (CNT) filled with ferromagnetic metals like iron, cobalt or nickel are new and very interesting nanostructured materials with a number of unique properties. In this paper we give an overview about different chemical vapor deposition (CVD) methods for their synthesis and discuss the influence of selected growth parameters. In addition we evaluate possible growth mechanisms involved in their formation. Moreover we show their identified structural and magnetic properties. On the basis of these properties we present different application possibilities. Some selected examples reveal the high potential of these materials in the field of medicine and nanotechnology.

Biocompatibility of iron filled carbon nanotubes in vitro.

Due to their particular magnetic properties, nanoparticles of metallic iron are promising candidates for magnetic fluid hyperthermia when compared to the commonly used iron oxides. However, the difficulty of handling these structures in ambient conditions without oxidation hinders its practical application. In this work, iron filled carbon nanotubes non-covalently functionalized by human serum albumin are studied as potential agents for hyperthermia. Here the iron is encapsulated inside of the carbon shells and protected from reactions with its environment. Besides protecting the iron and biological environment against each other, the carbon shells can also work as an interface for conjugation with other biological molecules of interest. In order to assess if such structures could induce any toxic effect in human cell cultures, we have probed its biocompatibility on a dosage and time dependent manner by measuring metabolic activity, cell proliferation, cell cycle distribution and apoptosis. Our results have shown that those nanotubes strongly associate with cells within a short incubation period and do not pose any significant toxic effect. The magnetic properties of iron filled carbon nanotubes in biological environment, i.e., associated to cells, have been studied and a possible rotation as a function of the applied magnetic field is discussed. Our initial findings encourage the further study of these structures as potential hyperthermia agents.

Stepwise current-driven release of attogram quantities of copper iodide encapsulated in carbon nanotubes.

Encapsulated nanograins of copper iodide have been sequentially discharged from individual carbon nanotubes. Using a high resolution electron microscope equipped with a two-terminal electrical measurements unit, it was possible to manipulate the filling contents with precisions of a few attograms at a time. Changes in electrical resistance and filling ratio were followed in tandem and in real-time. It is shown that the pulsed release of the halide is directly related to the overall conductance of the filled nanotube.

A carbon-wrapped nanoscaled thermometer for temperature control in biological environments.

AIMS: A carbon-wrapped nanoscaled thermometer for a contactless temperature control in biological systems on the cellular level is presented. MATERIALS & METHODS: The thermometer is based on multiwalled carbon nanotubes (MWCNTs) filled with materials with strongly temperature-dependent nuclear magnetic resonance (NMR) parameters. The NMR frequency shift and relaxation time were measured in cuprous-iodide-filled CNTs at different temperatures. RESULTS: The experimental data indicate a pronounced temperature dependence of the NMR parameters, thereby realizing the nanoscaled thermometer. CONCLUSION: This study is a proof-of-concept that the functionalized CNTs can be used as a contactless thermometer in biomedical applications.

Carbon nanotubes filled with a chemotherapeutic agent: a nanocarrier mediates inhibition of tumor cell growth.

AIM: In this paper, carbon nanotubes (CNTs) are presented as feasible carriers for carboplatin, a therapeutic agent for cancer treatment. The drug was introduced into CNTs to demonstrate that they are suited as nanocontainers and nanocarriers and can release the drug to initialize its medical virtue. METHOD: The filling was accomplished by a wet-chemical approach after the CNTs were opened. The effect on cell proliferation and cytotoxicity of the carboplatin-filled CNT was investigated by using a viability assays. RESULTS: Using different analysis methods such as electron energy loss spectroscopy and x-ray photoelectron spectroscopy the structure of carboplatin incorporated into the CNTs was found to be retained. In vitro studies showed that carboplatin-filled CNTs inhibited growth of bladder cancer cells whereas unfilled, opened CNTs barely affected cancer cell growth. CONCLUSION: A reversible filling-emptying process could be performed successfully within this work. This highlights the potential of CNTs for applications in the field of drug delivery.

Thermal decomposition of ferrocene as a method for production of single-walled carbon nanotubes without additional carbon sources.

A new method to grow bulk quantities of single-walled carbon nanotubes (SWCNTs) by a catalytic chemical vapor deposition (CVD) process with the possibility of varying the pressure has been developed and is reported in this paper. Thermal decomposition of ferrocene provides both catalytic particles and carbon sources for SWCNT growth using Ar as a carrier gas. Upon an increase in the pressure, the mean diameter of the SWCNTs decreases. In fact, high abundances of SWCNT with diameters as small as 0.7 nm, which is the limit for stable caps with isolated pentagons, can be obtained. An additional advantage of this method is that as no external carbon sources are required, SWCNT synthesis can be achieved at temperatures as low as 650 degrees C.