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Multi-walled carbon nanotubes (MWCNTs) are composed of multiple coaxially arranged graphene cylinders. MWCNTs range in diameter from 1 to over 100 nm depending on the number of constituting graphene cylinders. MWCNTs can be divided into two general subtypes, straight and tangled: increasing the number of constituent graphene cylinders increases the number of layers that compose the carbon nanotube wall, and as the number of wall layers increase, the wall thickness increases and the MWCNT becomes more rigid and straight. MWCNTs with a low number of wall layers are flexible and can assemble into tangled agglomerates. We initially showed MWCNT-N, a straight-type MWCNT with 30-40 walls, induced lung tumors and mesotheliomas after administration by intra-tracheal intra-pulmonary spraying (TIPS): rats were administered a total dose of 1mg/rat during the initial 2 weeks of the study, and animals were observed for 2 years without any further treatments. Using this short-term dosing and 2-year observation method we conducted carcinogenicity tests for other MWCNTs with different cylinder wall layers. We found that both straight type MWCNTs, MWCNT-7 (40 layers), MWCNT-A (150 layers), and tangled type MWCNTs, MWCNT-B (15 layers) and double-walled CNT (DWCNT) (2 layers) induced lung tumors and/or pleural mesotheliomas. In contrast to these results, we found carbon nanohorns, carbon nanostructures composed of single-walled carbon nanotubes (SWCNT), and carbon nanobrushes, a fibrous aggregate of carbon nanohorns, were not carcinogenic. Data on foreign body radical production, microarray and mutational signature analyses, and gene alterations will be presented.

In the process of bone metastasis, tumor cells spread to the bones to activate osteoclasts, which cause pathological bone resorption and destruction. Bisphosphonates (BPs) inhibit osteoclast activation to resorb bone, reducing bone pain and fracture. We previously developed a nanocomposite for potential localized treatment of bone metastasis by loading a BP compound, ibandronate, onto oxidized carbon nanohorns (OxCNHs), a next-generation drug carrier, using calcium phosphates (CaPs) as mediators to generate OxCNH-CaP-BP nanocomposites. The objective of the present study was to determine nanocomposite formation and biological properties of nanocomposites constructed from two BPs, zoledronate and pamidronate.

Thermogenesis via fatty acid-induced uncoupled mitochondrial respiration is the primary function of brown adipose tissue (BAT). In response to changes in ambient temperatures, the weight and specific gravity of BAT change, depending on the quantity of lipid droplets stored in brown adipocytes (BA). Such conditions should result in the reconstruction of connective tissue skeletons, especially of collagen fiber networks, although the mechanisms have not been clarified. This study showed that, within 4 hr of exposing mice to a cold environment, collagen fibers in the extracellular matrix (ECM) of BAT became discontinuous, twisted, emancipated, and curtailed. Surprisingly, the structure of collagen fibers returned to normal after the mice were kept at room temperature for 19 hr, indicating that the alterations in collagen fiber structures are physiological processes association with adaptation to cold environments. These dynamic changes in connective tissue skeletons were not observed in white adipose tissues, suggesting that they are unique to BAT. Interestingly, the vascular permeability of BAT was also augmented by exposure to cold. Collectively, these findings indicate that dynamic changes in ECM collagen fibers provide high flexibility to BAT, enabling the adjustment of tissue structures and the regulation of vascular permeability, resulting in adaptation to changes in ambient temperatures.

Carbon nanohorns (CNHs), a type of nanocarbon, have been studied for the application of drug delivery systems (DDSs) because they are easily functionalized, support bone regeneration, can be used to perform photohyperthermia, have low toxicity, and are easily phagocytosed by macrophages. To take advantage of these features of CNHs, we developed a DDS for the local treatment of bone metastasis by loading the antibone resorption drug ibandronate (IBN) onto CNHs. The poor adsorption of IBN onto CNHs due to the weak hydrophilic-hydrophobic interaction was overcome by using calcium phosphates (CaPs) as mediators. In the fabrication process, we used oxidized CNH (OxCNH), which is less hydrophobic, onto which IBN was coprecipitated with CaP from a labile supersaturated CaP solution. OxCNH-CaP-IBN composite nanoparticles exerted stronger cell-suppressive effects than OxCNH and IBN in both murine macrophages (RAW264.7 cells) and osteoclasts (differentiated from RAW264.7 cells). OxCNH-CaP-IBN composite nanoparticles were efficiently phagocytosed by macrophage cells, where they specifically accumulated in lysosomes. The stronger cell-suppressive effects were likely due to intracellular delivery of IBN, i.e., the release of IBN from OxCNH-CaP-IBN composite nanoparticles via dissociation of CaP in the acidic environment of lysosomes. Our findings suggest that OxCNH-CaP-IBN composite nanoparticles are potentially useful for the local treatment of metastatic bone destruction.

This work demonstrates that certain medically-approved drugs possess dual functions such that they exhibit intrinsic drug effects and can assist in dispersing carbon nanomaterials. Two types of carbon nanohorns (CNHs) (unoxidized: as-CNH, oxidized: CNHox550) and carbon nanotubes (CNTs) were successfully dispersed in aqueous solutions using minocycline (MC) as a dispersant. Absorption spectra, thermogravimetric analyses and theoretical calculations demonstrated that the MC was attached to the CNHs in these dispersions. The antibacterial activities of these MC/CNH complexes were examined using Streptcoccus mutans and Aggregatibacter actinomycetemcomitans, and the MC/as-CNH complex was found to maintain the same bacterial growth inhibition activity as the original MC. Electron microscopy observations suggested direct contact of the MC/CNH complexes with the bacteria, presumably allowing delivery of the MC. The results obtained from our study demonstrate that drug/nanocarbon complexes have potential applications in drug delivery.

Photoluminescence (PL) of single-walled carbon nanotubes (SWCNTs) in the near-infrared (NIR) region (E11 emission) is attractive, especially for bioimaging and biosensing in vivo because of the goo...

The gel column chromatography method allows high-throughput and high-purity single-wall carbon nanotube (SWCNT) separation. However, the role of the gel in this system has not been fully understood. In this study, five gels with different dextran concentrations were synthesized by directly crosslinking dextran with epichlorohydrin. The low dextran concentration gels work for metal/semiconductor separation and diameter sorting of semiconducting SWCNTs. This is evidence that the chemical structure in the gel that is responsible for the selective adsorption of semiconducting SWCNTs is dextran. However, high dextran concentration gels did not adsorb SWCNTs, although the adsorption site was dextran. Micro-Raman measurements on gel slices revealed that the high dextran concentration gel has a pore size too small to allow deep diffusion of SWCNTs. Not only the chemical structure but also the physical structure is important for designing high-performance gels for SWCNT separation in the near future.

Understanding the biodegradation profiles of various types of carbon nanotubes (CNTs) is important for their safe use according to their structural characteristics. To investigate the relationship between the biodegradation and the physicochemical properties of CNTs, sodium hypochlorite was used to degrade CNTs because it is believed to be a key oxidizer of CNTs inside macrophages and neutrophils. The complete degradation of CNTs in response to sodium hypochlorite was confirmed, and the half-lives of 11 different types of commercially available single-wall CNTs (SWNTs), carbon nanohorns (CNHs), and multiwall CNTs (MWNTs) in sodium hypochlorite were determined. The degradation of CNTs generally correlated with diameter, as follows: SWNTs ≥ CNHs > thinner MWNTs > thicker MWNTs. In addition, defects and the degree of dispersion also affected the degradation rate, but these were not the primary factors determining CNT degradation.

Introduction and objective: With the increase in carbon nanotube-based products on the commercial market, public concern regarding the possible toxicity of these nanomaterials has attracted much attention. Although previous studies found no obvious toxicity related to carbon nanotubes (CNTs), their safety has not been established because long-term evaluation is still needed. In vitro assays are used to understand the toxicity of nanomaterials. However, the data published so far were generated in short-term assays in which cells are continuously exposed to CNTs. Therefore, the objective of this study is to quantitatively assess the relative long-term cytotoxicity and degradation of CNTs after uptake by macrophages. Methods: We used macrophage cell line of RAW 264.7 and primary rat Kupffer cells to investigate macrophage uptake of CNTs as well as their quantity changes up to a relatively late time point after uptake (7 days) by measuring optical absorbance in the near infrared region and Raman spectra of CNTs in the cell lysates. The time-dependent cytotoxicity was evaluated by measuring reactive oxygen species (ROS), glutathione, cell viability, and caspase 3/7 activity in 1–7 days. Results: CNTs were degraded by approximately 25–30% within first 4 days after uptake; however, and no additional degradation occurred for the remainder of the 7-day test period. Generation of ROS by macrophages decreased as CNT degradation occurred, returning to control levels by Day 7. In the meantime, the glutathione level gradually recovered over time. There were no changes in cell viability or caspase 3/7 activation during CNT degradation. Conclusion: These results confirm that degradation of CNTs by macrophages is associated with ROS generation. The data also suggest that CNT cytotoxicity decreases as they are degraded.

Carbon nanomaterials (CNMs) are used in various functional materials and products as well as in basic research, predominantly in engineering. Because of their high biocompatibility, use of CNMs in bioapplications is widely anticipated. Many researchers have examined the kinetics and toxicity of intravenously administered CNMs. However, little research on the in vivo kinetics of locally implanted CNMs has been reported. In this study, single-walled carbon nanotubes (SWCNTs) were implanted between the periosteum and parietal bone of mice. The in vivo kinetics of the implanted SWCNTs were observed by near-infrared (NIR) fluorescence imaging (excitation wavelength, 730 nm; emission wavelength, >1000 nm), because the body is highly transparent to light in the NIR region, and autofluorescence in this region is low, making NIR fluorescence suitable for bioimaging. SWCNTs were visible in the subcutaneous tissue and medullary cavity. Fluorescence was observed in the cranial region, and its intensity gradually decr...

The present study compared the effects of two commonly-used dispersants, bovine serum albumin (BSA) and polyethylene glycol (PEG), on the biodistribution and toxicity of oxidized super-growth single-wall carbon nanotubes (oxSG) injected intravenously into mice over 3 months. About 1-2% of the injected dose (ID) of oxSG dispersed in BSA (oxSG-BSA) was present in the lungs at all time points. By contrast, about 15% of the ID of oxSG dispersed in PEG (oxSG-PEG) was present in the lungs at 1 day (D1), with accumulation decreasing to about 5% of the ID at 90 days (D90). About 70-80% of the IDs of both oxSG-BSA and oxSG-PEG were present in the liver at D1; by D90, about 15% of the IDs were cleared slowly (oxSG-BSA) or rapidly (oxSG-PEG). In the spleen, about 7% of the IDs of both oxSG-BSA and oxSG-PEG were present at all time points. The toxicities of oxSG-BSA and oxSG-PEG were comparable: no obvious signs of inflammation were observed on histological assessments of the lungs, liver, and spleen and on measurements of cytokine activity in blood plasma and tissue lysates. Concentrations of aspartate transaminase slightly increased at some time points in blood plasma, suggesting that oxSG-BSA and oxSG-PEG were slightly hepatoxic. Taken together, these results indicated that the dispersants had limited effect on the biodistribution and toxicity of oxSGs.

Fibrous aggregates of single-walled carbon nanohorns (carbon nanobrushes: CNBs) were prepared by CO2 laser ablation of an iron-containing carbon target with rotations under nitrogen atmosphere and ambient pressure. The rotation speed of the target and concentration of iron contained in it were controlled so as to increase the yield of CNBs. As a result, many CNBs were obtained at a rotation speed of 1 rpm and iron concentration above 1 at. %, although the samples still contained spherical single-walled carbon nanohorn aggregates (CNHs). The sheet resistivity of the samples containing both CNBs and CNHs decreased with the CNB content, which indicates that the CNBs formed a good conducting path. By forming supercapacitor electrodes, the capacitances of mixture of CNBs and CNHs, CNHs, and activated carbon were similar, i.e., 20, 21, and 23 F/g, respectively, at 0.1 A/g. However, the capacitance of the mixture of CNBs and CNHs at a discharge current of 5 A/g was about 1.4 and 6 times higher than that of the CNHs and activated carbon. These newly discovered CNBs should definitely increase the advantages of nanocarbon in various fields, especially in electronic devices.

Brown adipose tissue (BAT), which is composed of thermogenic brown adipocytes (BA) and non-parenchymal components including vasculatures and extracellular matrix, contribute to the maintenance of body temperature. BAT distribution is detected by positron emission tomography-computed tomography (PET/CT) using 18F-fluorodeoxy glucose (18F-FDG) or single-photon-emission computed tomography-computed tomography (SPECT/CT) using [123/125I]-beta-methyl-p-iodophenyl-pentadecanoic acid. Although sympathetic nerve activity and thermogenic capacity of BA is downregulated under fasting conditions in mice, fasting-dependent structural changes and fluid kinetics of BAT remain unknown. Here we show that the fasting induces fine and reversible structural changes in the non-parenchymal region in murine BAT with widened intercellular spaces and deformed collagen bands as revealed by electron microscopy. Interestingly, a newly introduced near infrared fluorescent probe of single-walled carbon nanotubes (CNTs) coated with phospholipid polyethylene glycol (PLPEG) easily demonstrated enhanced vascular permeability in BAT by the fasting. PLPEG-CNTs extravasated and remained in intercellular spaces or further redistributed in parenchymal cells in fasted mice, which is a previously unknown phenomenon. Thus, PLPEG-CNTs provide a powerful tool to trace fluid kinetics in sub-tissue levels.

Katsutoshi Kokubun,1,2 Sachiko Matsumura,1 Masako Yudasaka,3,4 Sumio Iijima,3,4 Kiyotaka Shiba1 1Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan; 3Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan; 4Graduate School of Science and Technology, Meijo University, Nagoya, Japan Introduction: Inorganic materials are widely used in medical devices, such as artificial hearts, vessels, and joints, in stents, and as nanocarriers for drug-delivery systems. Carbon nanomaterials are of particular interest due to their biological inertness and their capability to accommodate molecules. Several attempts have been proposed, in which carbon nanomaterials are used as nanocarriers for the systemic delivery of drugs.Materials and methods: We developed a drug-delivery system in which oxidized single-walled carbon nanohorns (oxSWNHs) were immobilized on a titanium (Ti) surface using material-binding peptides to enable localized drug delivery. For this purpose, we utilized a bispecific peptidic aptamer comprising a core sequence of a Ti-binding peptide and a SWNH-binding peptide to immobilize oxSWNHs on Ti.Results: Scanning electron microscopy was used to confirm the presence of oxSWNHs adsorbed onto the Ti surface, and a quartz crystal microbalance was used to evaluate the binding process during oxSWNH adsorption. The oxSWNHs-ornamented Ti substrate was nontoxic to cells and released biologically active dexamethasone over a sustained period.Conclusion: This oxSWNHs-immobilized system can be used to modify the surface of Ti in implants and be loaded with drugs that stimulate osteogenesis and bone regeneration. Keywords: drug carrier, drug delivery, carbon nanomaterial, carbon nanohorn, peptide aptamer

Quantification of the cellular uptake of nanomaterials is crucial for studies of their toxicity and medical applications. However, our knowledge of the behaviors of carbon nanotubes (CNTs) in cells or tissues remains incomplete due to the lack of appropriate methods for quantitative analysis. Here, we present a unique methodology for quantitatively assessing the cellular uptake of CNTs, taking advantage of their absorption of light in the near-infrared region. Measurement of CNT concentration in cell lysates by monitoring absorbance at 750 nm enabled highly accurate quantification of CNTs accumulated within cells. In a comparative study of eight commercially available CNTs with dynamic size ranging from 30 to 400 nm, we obtained the first quantitative evidence that cellular uptake of CNTs by RAW264.7 macrophages depends on their sizes, specifically on the widths of their bundles in dispersion, regardless of type or manufacturer. Specifically, uptake of CNTs increased linearly with dynamic size, and cytotoxicity increased along with uptake.

Cores of fibrous aggregates composed of radially assembled graphene-based single-walled carbon nanohorns, named as carbon nanobrushes (CNBs), were observed using electron microscopes. As a result, a carbon nanotube (CNT), probably single-layer structure, exposed from the CNBs was observed. From cross section images of CNBs, three round structures of about 2.5 nm diameters were also observed clearly at center part of single-walled carbon nanohorn (SWCNH) aggregate, which indicates the cross section of bundled single-walled CNTs. Therefore, we found that CNTs were localized at the core of CNBs. From these results, as for the formation mechanism of CNBs, it is supposed that the CNT functions as a template and SWCNHs radially gather on the CNT.

In biological studies, phospholipid poly(ethylene glycol) (PLPEG) is used to disperse nanocarbons, which effectively reduces the macrophage uptake of nanocarbons. Single-walled carbon nanohorn (CNH), a type of nanocarbon, was dispersed with PLPEG in this study, and the effect of PLPEG quantity on the cytotoxicity of PLPEG-CNH in RAW264.7 mouse macrophages was revealed. The results were compared with the macrophage uptake quantity of PLPEG-CNH or agglomeration size of PLPEG-CNH. It is concluded that the optimum PLPEG:CNH weight ratio was 0.5:1 and 1:1. At the higher or lower ratios, the PLPEG-CNH toxicity and the macrophage uptake quantity increased and large agglomerates appeared. These tendencies at the lower PLPEG:CNH ratio were caused by the CNHs surfaces not being sufficiently well covered by PLPEG. The tendency at the higher PLPEG:CNH ratio was curious, for which we deduced that PLPEG adsorbed on CNHs was detached to form micelles, leading to the reappearance of the CNHs not well covered with PLPEG.

Based on the characteristics of carbon nanotubes (CNTs) that absorb light in the near-infrared region, we have developed a method to quantify the biodistribution of CNTs in mouse tissues such as the liver, lungs and spleen. By using this method, the kinetic biodistribution of single-walled CNTs (SWNTs) after intravenous injection into mice for 60 days has been successfully investigated. The results show that the biodistribution of CNTs was diameter-dependent by comparing two different diameters of SWNTs. The SWNTs with larger diameters (1–5 nm) accumulated more in the liver or spleen but less in the lungs than those with smaller diameters (0.7–0.9 nm). The quantities of both SWNTs in the liver and lungs decreased with time and showed no significant change in the spleen, which is also confirmed by histological analysis. In particular, the results have demonstrated that both SWNTs are cleared from the lungs almost completely within 60 days, suggesting that the pulmonary toxicity of SWNTs would be low when low amounts of CNTs (

In the present work, the convergence of two different drug delivery systems is investigated, namely the combination of carbon nanohorns (CNHs) and liposomes. Our effort initially included the synthesis of two conversely charged carbon nanohorns and their subsequent analysis through various methods. The study of their effect on the thermotropic behavior of artificial membranes provided an essential assistance for the upcoming liposome preparation, which were estimated for their physicochemical properties. The presence of CNHs alters the calorimetric parameters of the lipids. We also prepared CNHs:liposome systems. The characteristic morphology and secondary spherical superstructure of CNHs is retained in the chimeric materials, suggesting that the interactions with the liposomes do not alter the dahlia-flower-like aggregation of CNHs. Both CNHs-liposome systems exhibit a relatively small cellular cytotoxicity in vitro, tested in mouse embryonic fibroblasts. To summarize, we developed CNHs:liposome platforms with a complete knowledge of their thermotropic, physicochemical, morphological and nanotoxicological characteristics.

Photoluminescence (PL) in the near-infrared (NIR) region is an attractive feature of single-walled carbon nanotubes (SWNTs). In this study, we investigated the effect of the chemical structure of the cross-linked polymer coating of polymer-coated SWNTs on the NIR PL emission intensity. We found that brighter NIR emission can be achieved using a more hydrophobic polymer coating.

Single-walled carbon nanotubes (SWCNTs) show strong fluorescence in the 1000-1700 nm second near-infrared (NIR-II) wavelength range and are considered promising candidates for angiographic imaging probes. Oxygen-doped SWCNTs coated with phospholipid-polyethylene glycol (o-SWCNT-PEG) show exceptional potential, as they emit fluorescence at ∼1300 nm through excitation with 980 nm light. Here, with the aim of putting o-SWCNTs to practical use as an angiographic agent in animal experiments, the retention time after intravenous administration in the vasculature of mice and the biodistribution were studied. To provide bio affinity, the o-SWCNTs were coated with phospholipid polyethylene glycol. The intravenously injected o-SWCNT-PEG circulated within the vasculature for 3 h and cleared within 1 day. There was prominent fluorescence and Raman signals from the SWCNTs in the liver and spleen early in the experiment; the signals remained for 1 month. No apparent abnormalities in weight or appearance were observed after 2 months, suggesting low toxicity of o-SWCNT-PEG. These characteristics of o-SWCNT-PEG would make it useful as an angiographic imaging probe in the NIR-II wavelength range.

Carbon nanotubes (CNTs) have been applied in a wide range of fields, such as materials, electronics, energy storages, and biomedicine. With the rapid increase in CNTs industrialization, more and more CNT-containing wastewater is being produced. Since concerns about the toxic effects of CNTs on human health persist, CNT-containing wastewater should not be released into the environment without purification, but no effective methods have been reported. In the present study, we report a simple method to eliminate CNTs from industrial or laboratorial wastewater using sodium hypochlorite. Direct treatment of aqueous dispersions with sodium hypochlorite solution completely degraded CNTs into carbon oxides or carbonates ions. Since hypochlorite is environmentally friendly and frequently used as a disinfectant or bleaching agent in domestic cleaning, this method is practical for purification of CNT-contaminated industrial wastewater.

Boron- and nitrogen-codoped single walled carbon nanohorns (BN-SWCNHs) were prepared by CO 2 laser ablation of a boron-containing carbon target under nitrogen atmosphere. The structures were spherical SWCNH aggregates containing many graphite-like thin sheets (GLSs), which was different from general SWCNHs. X-ray photoelectron spectra indicated that the doped quantities of boron and nitrogen were about 1.2 and 1.0 at.%, respectively. The boron and nitrogen atoms were implanted partially as the BN bonding in a graphene lattice, although they were also implanted individually as three-fold coordinated sp 2 bonding. The boron-doped GLSs were preferentially prepared by CO 2 laser ablation of a boron-containing carbon target under argon atmospheres. As a result, we found that the boron accelerated the formation of GLSs. The simple CO 2 laser ablation method will be useful for heteroatoms doping into carbon nanohorns.

Adsorption of polyethylene glycol conjugated phospholipids with various PEG chain length (DSPE-PEG5000, 2000, 750) onto single-walled carbon nanohorns (SWCNH), a type of graphene nano-tubule, in aqueous solution was investigated by means of high-resolution magic angle spinning (HRMAS) 1H NMR. Peak integral ratio of PEG chains and alkyl chains of DSPE-PEGs in the NMR spectra linearly decreased to zero with the increase of SWCNH quantity, indicating that the adsorption of DSPE-PEGs on SWCNH was virtually irreversible. The area of SWCNH surface allocated to the individual DSPE-PEG5000, 2000, 750 molecule were estimated to be 7.06, 5.18, and 4.45 nm2, respectively. Coverages of the alkyl chains on the surface area of SWCNH were about 28%, 39% for DSPE-PEG5000, 2000 and 46% for DSPE-PEG750, suggesting single layer adsorption. We presumed that the electrostatic repulsion may prevent DSPE-PEGs from multiple layer and keep away neighbouring DSPE-PEGs on the surface. According to the molecular areas of the DSPE-PEGs, PEG5000 and 2000 chains were considered to be in brush-regimes, while PEG750 was considered to be in mushroom regime on the SWCNH surface.

We have developed multi-componential nanomaterials that are based on folic acid (FA) and polyethylenimine-functionalized carbon nanohorn conjugates that encapsulate magnetite nanoparticles. The nanoconjugates were characterized using a variety of experimental setups, including dynamic light scattering, thermogravimetric analysis, Fourier transform infrared spectrometry, and ultraviolet–visible–near-infrared (UV–Vis–NIR) spectroscopy. An NIR laser and a radio frequency-induction heating system were used to evaluate the heat-generating capability of the nanoconjugates. Aqueous solutions containing the nanoconjugates exhibited a significant increase in temperature after laser irradiation and/or radio frequency induction compared with controls. The intercellular distribution of the nanoconjugates was quantitatively analyzed using UV–Vis–NIR spectroscopy with two cell lines: human epidermal carcinoma (KB) and human embryonic (FHs173We) cells. The interaction between the FA-modified nanoconjugates and KB cells was enhanced through overexpression of FA receptors on the surface of the KB cells. A stronger interaction between the nanoconjugates and KB cells was observed in the presence of a magnet. Furthermore, laser- and/or radio frequency-induced nanoconjugates in combination with external magnetic application reduced the viability of KB cells. Therefore, the present study will open a new direction for the development of multi-dimensional cancer therapy.

The biodistribution of single-walled carbon nanotubes (CNTs) was quantified after intravenous administration to mice based on their absorption of near-infrared light. CNTs with two different diameters, 1–5 nm (Ld-CNT) or 0.7–0.9 nm (Sd-CNT), were compared. The accumulation of Ld-CNTs in the lung was less than that of Sd-CNTs, and both were cleared almost completely within 60 days. The rapid clearance of CNTs could be due to their degradation by macrophages and/or to their trafficking to other organs via the vasculature. In the liver and spleen, the accumulation of Ld-CNTs was greater than that of Sd-CNTs. The quantity of Ld- or Sd-CNTs in the liver decreased for about 10% of the dose in 60 days. These results were confirmed by histological analysis. Levels of the cytokines TGF-β1, IL-6, INF-γ, and TNF-α in the plasma and organs of mice injected with Ld- and Sd-CNTs were low, suggesting the low toxicity of Ld- and Sd-CNTs.

Introduction and objective: With the increase in carbon nanotube-based products on the commercial market, public concern regarding the possible toxicity of these nanomaterials has attracted much attention. Although previous studies found no obvious toxicity related to carbon nanotubes (CNTs), their safety has not been established because long-term evaluation is still needed. In vitro assays are used to understand the toxicity of nanomaterials. However, the data published so far were generated in short-term assays in which cells are continuously exposed to CNTs. Therefore, the objective of this study is to quantitatively assess the relative long-term cytotoxicity and degradation of CNTs after uptake by macrophages. Methods: We used macrophage cell line of RAW 264.7 and primary rat Kupffer cells to investigate macrophage uptake of CNTs as well as their quantity changes up to a relatively late time point after uptake (7 days) by measuring optical absorbance in the near infrared region and Raman spectra of CNTs in the cell lysates. The time-dependent cytotoxicity was evaluated by measuring reactive oxygen species (ROS), glutathione, cell viability, and caspase 3/7 activity in 1–7 days. Results: CNTs were degraded by approximately 25–30% within first 4 days after uptake; however, and no additional degradation occurred for the remainder of the 7-day test period. Generation of ROS by macrophages decreased as CNT degradation occurred, returning to control levels by Day 7. In the meantime, the glutathione level gradually recovered over time. There were no changes in cell viability or caspase 3/7 activation during CNT degradation. Conclusion: These results confirm that degradation of CNTs by macrophages is associated with ROS generation. The data also suggest that CNT cytotoxicity decreases as they are degraded.

Chemical modification of carbon nanotube surface can controllably modulate their optical properties. Here we report a simple and effective synthesis method of oxygen-doped single-walled carbon nanotubes (o-SWCNTs), in which a thin film of SWCNTs is just irradiated under the UV light for a few minutes in air. By using this method, the epoxide-type oxygen-adducts (ep-SWCNTs) were produced in addition to the ether-type oxygen-adducts (eth-SWCNTs). The Treated (6, 5) ep-SWCNTs show a red-shifted luminescence at ~1280 nm, which corresponds to the most transparent regions for bio-materials. Immunoassay, fluorescence vascular angiography and observation of the intestinal contractile activity of mice were demonstrated by using the produced o-SWCNTs as infrared fluorescent labels and imaging agents.

The covalent functionalization of carbon nanohorns (CNHs) via the 1,3-dipolar cycloaddition reaction of azomethine ylides generated by the thermal ring opening of aziridines bearing electron-withdrawing substituents is described. This is a complementary methodology, to the in situ generated azomethine ylides derived upon the thermal decarboxylation of immonium salts originated from condensation of α-aminoacids with aldehydes, for the surface modification of CNHs. The modified CNHs featuring pyrrolidine rings fused to the junction between two six-membered rings of CNHs 4a and 4b were characterized by Raman and ATR-IR spectroscopy as well as DLS, while imaged by HR-TEM microscopy and the loading of the organic addends was calculated by thermogravimetry. Furthermore, gold nanoparticles were grown and immobilized on CNH-based material 4b, yielding pyrrolidino-modified CNH/Aunano hybrid material 5, which was additionally imaged by STEM-ADF to identify the presence of gold nanoparticles as verified by EDX spectroscopy analysis.

Building all-carbon based functional materials for light energy harvesting applications could be a solution to tackle and reduce environmental carbon output. However, development of such all-carbon based donor-acceptor hybrids and demonstration of photoinduced charge separation in such nanohybrids is a challenge since in these hybrids part of the carbon material should act as an electron donating or accepting photosensitizer while the second part should fulfil the role of an electron acceptor or donor. In the present work, we have successfully addressed this issue by synthesizing covalently linked all-carbon-based donor-acceptor nanoensembles using single-walled carbon nanotubes (SWCNTs) as the donor and C60 as an acceptor. The donor-acceptor entities in the nanoensembles were connected by phenylene-ethynylene spacer units to achieve better electronic communication and to vary the distance between the components. These novel SWCNT-C60 nanoensembles have been characterized by a number of techniques, including TGA, FT-IR, Raman, AFM, absorbance and electrochemical methods. The moderate number of fullerene addends present on the side-walls of the nanotubes largely preserved the electronic structure of the nanotubes. The thermodynamic feasibility of charge separation in these nanoensembles was established using spectral and electrochemical data. Finally, occurrence of ultrafast electron transfer from the excited nanotubes in these donor-acceptor nanohybrids has been established from femtosecond transient absorption studies, signifying their utility in building light energy harvesting devices.

By using carbon nanohorns as starting materials, small- and uniform-sized graphene oxide (S-GO) sheets can be prepared in high yields via an oxidation method. The obtained S-GO sheets have a band-like structure with a length of 20-50 nm, a width of 2-10 nm, and a thickness of 0.5-5 nm. S-GO sheets are hydrophilic due to abundant oxygenated groups on the surfaces and edges; hence, this nanomaterial is highly dispersive in aqueous solutions and some hydrophilic organic solvents. Additionally, like other S-GO samples, the S-GO sheets prepared here are strongly fluorescent over the visible light wavelength region. These characteristics underscore the high potential of S-GO sheets for nanomedical and diagnostic applications. In proof-of-concept experiments, the S-GO sheets were conjugated with an arginine-glycine-aspartic acid derivative for tumour-targeting drug delivery applications, and with an immunoglobulin G antibody for immunoassay applications.

Boron neutron capture therapy requires boron carriers that can deliver abundant boron to tumors. To obtain such a carrier, we have prepared boron nitride (BN) containing carbon nanohorn aggregate (CNH) by heating CNHs with ammonia borane at 800 °C. The obtained BN-CNH had a C:B:N mole ratio of 5:2:2, as estimated from X-ray photoemission spectroscopy. The nanohorn tubule walls had graphene–BN double layers or BN–graphene–BN triple layers. The graphite-like sheets constituting the CNHs together with the nanohorn tubules also had BN layers on their surfaces. BN release from BN-CNH was small in cell culture medium, and about 70–80% of the BNs remained on the CNHs. For selective accumulation in tumor cells, the BN-CNH was coated with phospholipid polyethylene glycol having folate (BN-CNH/PLPEG-FA). In primary cell culture experiments, human tumor KB cells overexpressing FA receptors ingested more BN-CNH/PLPEG-FA than those without FA, while normal human FHs 173We cells did not show preferential uptake due to FA. The quantity of boron per cell exceeded the criteria required for boron neutron capture therapy by more than 100 times in the cell experiments. These results suggest that BN-CNH is potentially a good carrier for boron neutron capture therapy.

Nanopores (pores between 1 and 5 nm) have been the object of a great deal of attention because they can selectively adsorb relatively large molecules such as macromolecules and polymer molecules. Conventional methods for analyzing porous structures—such as N2 adsorption measurements at 77 K—can be used to investigate microporous and mesoporous structures, but there is a lack of investigation of nanopores or the boundary between micropores (

We have clarified that the electrical and thermal properties of single-walled carbon nanotubes (SWCNTs) are improved by multiple structural changes (wall number, diameter, and crystallinity) induced by high temperature treatment. Focusing on the relationship between structural change and electrical and thermal properties, high-purity SWCNTs were fabricated using the water-assisted CVD method and treated at high temperatures (1500–2000 °C) in an argon atmosphere. We showed that the electrical and thermal properties of the SWCNTs were improved by ∼2.9 and 3.0, respectively, which required lower treatment temperatures than for multi-walled CNTs (MWCNTs). In addition to the crystallinity improvement, the wall number and diameter increased with treatment temperature. When compared to as-grown SWCNTs of similar wall number and diameter, the heat treated SWCNTs exhibited higher electrical and thermal properties, which suggested that the property improvements could be attributed to not only to the wall number and diameter but also to the improvement in crystallinity.

Photothermal conversion of nanocarbons has potential applications in medical and energy engineering. It is expected that the photothermal conversion of tubular nanocarbons can thermally enhance polymer formation on their surfaces and insides. We show in this report that light irradiation enhanced the catalytic polymerization of caprolactone (CL) on tubular carbon nanohorns, and polycaprolactone (PCL) was formed on the outside and, more abundantly, inside the carbon nanohorns. The PCL particles were of nanometer size, which indicated another unique effect of this method of preparation. The abundant PCL preparation inside the nanohorns was probably caused by the confinement of CL molecules and thermal energies inside the nanohorns, which could enhance the polymerization of CLs. Other nanocarbons that had photothermal conversion properties would similarly enhance polymerization and other chemical reactions to provide unique methods of synthesizing materials.

We explore the importance of the size and position of nanoholes on the electrochemical performance of single-walled carbon nanohorn (SWCNH)-based supercapacitors using an ionic liquid electrolyte. The oxidized sample at 673 K showed a low specific capacitance per unit of internal specific surface area (4.0 μF cm–2), as the nanoholes created on the tips of SWCNHs via a selective chemical attack are too small to introduce electrolyte ions. For a sample oxidized at 723 K, the enlarged diameter of the nanoholes on the tips allows electrolyte ions to penetrate into the internal spaces of the SWCNHs, thereby resulting in a 2-fold capacitance improvement (8.6 μF cm–2). However, the abrupt decrease in the capacitance of the oxidized SWCNHs at 823 K (3.8 μF cm–2) can be explained by the selective formation of nanoholes on the sidewalls of the SWCNHs, where the small interstitial pores restrict ion diffusion to deeply positioned nanoholes on the sidewalls of the SWCNHs. Our study clearly reveals that the size and p...

Multifunctional nanomaterial-based probes have had key impacts on high-resolution and high-sensitivity bioimaging and therapeutics. Typically, NIR-absorbing metal sulfide-based nanocrystals (NCs) are highly assuring due to their unique optical properties. Yet, their in vivo behavior remains undetermined, which in turn undermines their potential bioapplications. Herein, we have examined the application of PEGylated Cu2S NCs as tumor contrast optical nanoprobes as well as investigated the short- and long-term in vivo compatibility focusing on anti-oxidant defense mechanism, genetic material, immune system, and vital organs. The studies revealed an overall safe profile of the NCs with no apparent toxicity even at longer exposure periods. The acquired observations culminate into a set of primary safety data of this nanomaterial and the use of PEGylated Cu2S NCs as promising optical nanoprobes with immense futuristic bioapplications.

The outer walls of double walled carbon nanotubes (DWCNTs) have been selectively functionalized with different substituted perylenediimides (PDIs) leaving the inner walls intact. The spacer connecting DWCNTs and PDIs, and the PDI macrocycle position has been varied to visualize the DWCNT-PDI interactions in the hybrids. Evidence of outer wall functionalization and the degree of PDI substitution on DWCNTs were arrived from HR-TEM, AFM, FTIR, TGA, XPS and Raman techniques while nanotube-photosentisizer interactions were probed from studies involving optical absorbance and emission, and electrochemical techniques. Fine-tuning of the electronic states of PDIs in the hybrids was possible with the present covalent approach. The fluorescence of PDIs in the hybrids was found to be quenched (60-70%) due to interactions with DWCNTs. Further, femtosecond transient absorption and photocatalytic electron pooling studies were performed to seek evidence of charge separation in these hybrids. In agreement with earlier studies, evidence of charge separation from the transient studies was bleak, and accordingly, yields of photocatalytic electron pooling were much lower than those reported earlier for fullerene and single walled carbon nanotube based hybrids. The present study is suggestive of further tuning of donor-acceptor energy levels in DWCNT derived hybrids for efficient charge separation and stabilization., This research was financially supported by the Spanish Ministry of Economy and Competitiveness (Mineco) of Spain (CTQ2013-48252-P and CTQ2011-26455), Junta de Comunidades de Castilla-La Mancha (PEII-2014-014-P), Generalitat Valenciana (PROMETEO 2012/010 and ISIC/2012/008) and the US-National Science Foundation (Grant No. 1401188 to FD). One of us (MB) thanks a FPI grant from Mineco.

Selective functionalization of the outer walls of double-walled carbon nanotubes (DWCNTs) with zinc and silicon phthalocyanines leaving the inner walls undamaged has been accomplished. The mode of metal phthalocyanine (MPc) connection was varied, that is, through the macrocycle periphery in the case of zinc phthalocyanines (ZnPcs) and through the silicon axial position in the case of silicon phthalocyanines (SiPcs) to visualize its effect on phthalocyanine–DWCNT interactions. Evidence of outer wall functionalization and the degree of phthalocyanine substitution on DWCNTs were arrived from HR-TEM, AFM, TGA, XPS and Raman techniques. The sensitizer-nanotube interactions were probed from studies involving optical absorbance, steady-state and time resolved emission, and electrochemical studies. The fluorescence of phthalocyanines in these hybrids was found to be almost quantitatively quenched (>95%) due to the interactions with DWCNTs, and such interactions were more for the SiPc derived hybrids. The femtosecond transient absorption studies performed revealed that the interactions are dynamic involving the singlet excited phthalocyanines and the nanotubes. In agreement with earlier studies, evidence for charge separation in these hybrids was bleak revealing weak signature bands of MPc˙+ in the 850 nm range. Additionally, the presence of trace amounts of single-walled carbon nanotubes in the hybrids further hampered detailed spectral analysis., This research was financially supported by the Spanish Ministry of Economy and Competitiveness (Mineco) of Spain (CTQ2011- 26455, CTQ2013-48252-P and CTQ2014-55798-R), Generalitat Valenciana (GVA) (Prometeo 2012/010), Junta de Comunidades Paper de Castilla-La Mancha (PEII-2014-014-P) and the US-National Science Foundation (Grant No. 1401188 to FD).

Carbon nanostructures are currently fuelling a revolution in science and technology in areas ranging from aerospace engineering to electronics. Oxidised carbon nanomaterials, such as graphene oxide, exhibit dramatically improved water dispersibility compared to their pristine equivalents, allowing their exploration in biology and medicine. Concomitant with these potential healthcare applications, the issue of degradability has been raised and has started to be investigated. The aim of the present study was to assess the potential of hypochlorite, a naturally occurring and industrially used ion, to degrade oxidised carbon nanomaterials within a week. Our main focus was to characterise the physical and chemical changes that occur during degradation of graphene oxide compared to two other oxidised carbon nanomaterials, namely carbon nanotubes and carbon nanohorns. The kinetics of degradation were closely monitored over a week using a battery of techniques including visual observation, UV-Vis spectroscopy, Raman spectroscopy, infrared spectroscopy, transmission electron microscopy and atomic force microscopy. Graphene oxide was rapidly degraded into a dominantly amorphous structure lacking the characteristic Raman signature and microscopic morphology. Oxidised carbon nanotubes underwent degradation via a wall exfoliation mechanism, yet maintained a large fraction of the sp2 carbon backbone, while the degradation of oxidised carbon nanohorns was somewhat intermediate. The present study shows the timeline of physical and chemical alterations of oxidised carbon nanomaterials, demonstrating a faster degradation of 2D graphene oxide sheets compared to 1D oxidised carbon nanomaterials over 7 days in the presence of an oxidising species.

Near-infrared photoluminescent single-walled carbon nanotubes (CNTs) are expected to provide effectual bio-imaging tools, although, as yet, only limited applications have been reported. Here, we report that CNTs coated with an amphiphilic and biocompatible polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate; PMB), generate high-quality images of brown fat. Brown fat is a heat-productive adipose tissue, which is attracting increasing attention as a new therapeutic target for obesity-associated metabolic disorders. Its brown colour is mainly attributed to densely packed capillaries, which facilitate its high heat-exchanging efficiency. Currently, positron emission tomography-computed tomography is the only practical technique to identify brown fat distribution in the living body; however, it is expensive to use. By virtue of their high affinity to apolipoproteins and exemption from macrophage phagocytosis, PMB-CNTs selectively accumulate on capillary endothelial cells but not larger vessels in adipose tissue. Therefore, the image brightness of adipose tissue can directly reflect the capillary density, and indirectly the thermogenic capability and brownness. PMB-CNTs provide clearer images than conventional organic dyes, as the high level of transmitted light passes through the body with less light scattering. Thus, PMB-CNT-based imaging methods could open a new phase in thermogenic adipose tissue research.

A single organism comprises diverse types of cells. To acquire a detailed understanding of the biological functions of each cell, comprehensive control and analysis of homeostatic processes at the single-cell level are required. In this study, we develop a new type of light-driven nanomodulator comprising dye-functionalized carbon nanohorns (CNHs) that generate heat and reactive oxygen species under biologically transparent near-infrared (NIR) laser irradiation. By exploiting the physicochemical properties of the nanohorns, cellular calcium ion flux and membrane currents were successfully controlled at the single-cell level. In addition, the nanomodulator allows a remote bioexcitation of tissues during NIR laser exposure making this system a powerful tool for single-cell analyses and innovative cell therapies. journal article 2014 Nov 24 2014 10 24 imported

Understanding the molecular mechanisms responsible for the cytotoxic effects of carbon nanomaterials is important for their future biomedical applications. Carbon nanotubular materials induce the generation of reactive oxygen species (ROS), which causes cell death; however, the exact details of this process are still unclear. Here, we identify a mechanism of ROS generation that is involved in the apoptosis of RAW264.7 macrophages caused by excess uptake of carbon nanohorns (CNHs), a typical type of carbon nanotubule. CNH accumulated in the lysosomes, where they induced lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteases, such as cathepsins, which in turn caused mitochondrial dysfunction and triggered the generation of ROS in the mitochondria. The nicotinamide adenine dinucleotide phosphate oxidase was not directly involved in CNH-related ROS production, and the ROS generation cannot be regulated by mitochondrial electron transport chain. ROS fed back to amplify the mitochondrial dysfunction, leading to the subsequent activation of caspases and cell apoptosis. Carbon nanotubules commonly accumulate in the lysosomes after internalization in cells; however, lysosomal dysfunction has not attracted much attention in toxicity studies of these materials. These results suggest that LMP, a neglected mechanism, may be the primary reason for carbon nanotubule toxicity.

Nitrogen-doped single wall carbon nanohorns (N-SWCNHs) were prepared by CO2 laser ablation of a graphite target under nitrogen atmosphere. X-ray photoelectron spectra showed that the doped nitrogen quantities were about 1.7 and 1.1 at.% under nitrogen and nitrogen/Ar mixed atmospheres, respectively. The nitrogen atoms were implicated as the pyridine-like and threefold coordinated sp2 bonding in graphene lattice of SWCNHs, and they were p-type dopants. The number of defect sites of N-SWCNHs was larger than that of SWCNHs prepared under Ar atmospheres, which was revealed by Raman and electron spin resonance measurements.

We describe in this work a novel electrochemical immunosensor design making use of carbon nanohorns (CNHs) as a scaffold for the preparation of disposable immunosensing platforms for the determination of fibrinogen (Fib). The approach involved the immobilization of Fib onto activated CNHs deposited on screen-printed carbon electrodes (SPCEs) and the implementation of an indirect competitive assay using anti-Fib labeled with horseradish peroxidase (HRP) and hydroquinone (HQ) as the redox mediator. Both CNHs and the Fib-CNHs covalent assembly were characterized by microscopic and electrochemical techniques. The different variables affecting the analytical performance of the amperometric immunosensing strategy were optimized. The calibration plot for Fib allowed a range of linearity between 0.1 and 100 μg/mL (r(2) = 0.994) and a detection limit of 58 ng/mL to be achieved. The Fib-CNHs/SPCEs exhibited an excellent storage stability of at least 42 days. The developed immunosensor provides, in general, an analytical performance better than that reported for other Fib immunosensors and commercial ELISA kits. This simple and relatively low cost immunosensor configuration permitted the sensitive and selective determination of Fib in human plasma and urine.