Raman spectroscopy using plasmonic and carbon-based nanoparticles for cancer detection, diagnosis, and treatment guidance.Part 1: Diagnosis.

Optical techniques, including Raman, photothermal and photoacoustic microscopy and spectroscopy, have been intensively explored for the sensitive and accurate detection of various diseases. Rapid advances in lasers, photodetectors, and nanotechnology have led to the development of Raman spectroscopy, particularly surface-enhanced Raman scattering (SERS), as a promising imaging modality that can help diagnose many diseases. This review focuses on the major recent advances in Raman spectroscopy and SERS-enhancing contrast nanoagents, as well as their potential to transition from a proof-of-concept approach to a cancer detection tool in vitro and in vivo.

Raman spectroscopy using plasmonic and carbon-based nanoparticles for cancer detection, diagnosis, and treatment guidance. Part 2: Treatment.

Raman spectroscopy and surface-enhanced raman scattering (SERS) have the potential to improve the detection and monitoring of various diseases, particularly cancer, with or without the support of multifunctional active nanosystems. This review is focused on the recent advances that have made Raman a major tool for treatment guidance for surgical tumor resection or for analytical monitoring of various therapies, such as photodynamic therapy, photothermal therapy, and drug delivery. The potential of Raman spectroscopy and nanosytems to further improve cancer treatments is also discussed.

Graphene-bimetallic nanoparticle composites with enhanced electro-catalytic detection of bisphenol A.

This study brings for the first time novel knowledge about the synthesis by catalytic chemical vapor deposition with induction heating of graphene-bimetallic nanoparticle composites (Gr-AuCu and Gr-AgCu) and their morphological and structural characterization by transmission electron microscopy, Raman spectroscopy, and x-ray powder diffraction. Gold electrodes modified with the obtained materials exhibit an enhanced electro-catalytic effect towards one of the most encountered estrogenic disruptive chemicals, bisphenol A (BPA). The BPA behavior in varying pH solutions was investigated using the electrochemical quartz crystal microbalance, which allowed the accurate determination of the number of molecules involved in the oxidation process. The modified electrodes promote the oxidation of BPA at significantly lower potentials (0.66 V) compared to bare gold (0.78 V). In addition, the peak current density recorded with such electrodes greatly exceeded that obtained with bare gold (e.g. one order of magnitude larger, for a Au/Gr-AgCu electrode). The two modified electrodes have low detection limits, of 1.31 × 10-6 M and 1.91 × 10-6 M for Au/Gr-AgCu and Au/Gr-AuCu, respectively. The bare gold electrode has a higher detection limit of 5.1 × 10-6 M. The effect of interfering species (e.g. catechol and 3-nitrophenol) was also investigated. Their presence influenced not only the BPA peak potential, but also the peak current. With both modified electrodes, no peak currents were recorded below 3 × 10-5 M BPA.

Raman spectroscopy analysis and mapping the biodistribution of inhaled carbon nanotubes in the lungs and blood of mice.

Because of their small size, robust structure and unique characteristics, carbon nanotubes (CNTs) are increasingly being used in a variety of biomedical applications, materials and products. As their use increases, so does the probability of their unintended release and human exposure. Therefore, it is important to establish their potential biodistribution and biopersistence to better understand the potential effects of their exposure to humans. This study examines the distribution of CNTs in CD-1 mice after exposure by inhalation of single-walled carbon nanotubes (SWCNTs) and investigates the possibility that inhaled nanoparticles could enter the circulatory system via the lungs. Raman spectroscopy was employed for the detection of CNTs in lung tissue and blood based on their unique spectroscopic signatures. These studies have important implications concerning the potential effects of exposure to SWCNTs and their use as potential transport vehicles in nanomedicine.

Novel multifunctional graphene sheets with encased Au/Ag nanoparticles for advanced electrochemical analysis of organic compounds.

This work is the first presentation of the synthesis of few-layer graphene decorated with gold and silver nanoparticles (Gr-Au-Ag) by chemical vapor deposition over a catalytic system formed of bimetallic Au-Ag nanoclusters supported on MgO and with methane used as the source of carbon. The sheetlike morphology of the graphene nanostructures, with mean sizes in the range of hundreds of nanometers, was observed by high-resolution electron microscopy. The distinctive feature found in all the samples was the regular rectangular or square shapes. This multi-component organic-inorganic nanomaterial was used to modify a platinum substrate and subsequently employed for the detection of carbamazepine, an anti-convulsion drug. UV/Vis spectroscopy revealed that a strong hypochromism occurred over time, after mixing solutions of graphene-Au-Ag with carbamazepine. This can be attributed to π-π stacking between the aromatic groups of the two compounds. Linear sweep voltammetry (LCV) provided evidence that the modified platinum substrate presented a significant electrocatalytic reaction toward the oxidation of carbamazepine. The intensity of the current was found to increase by up to 2.5 times, and the oxidation potential shifted from +1.5 to +1.35 V(Ag/AgCl) in comparison with the unmodified electrode. Electrochemical impedance spectroscopy (EIS) was further used to thoroughly assess the activity of the platinum electrode that was modified by the deposition of the Gr-Au-Ag composites in the presence of various concentrations of carbamazepine. The experimental EIS records were used for the generation of an equivalent electrical circuit, based on the charge-transfer resistance (R(ct)), Warburg impedance (Z(D)), solution resistance (R(s)), and a constant phase element (CPE) that characterizes the non-ideal interface capacitive responses.

Raman spectroscopy as a detection and analysis tool for in vitro specific targeting of pancreatic cancer cells by EGF-conjugated, single-walled carbon nanotubes.

Single-walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC-1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme-linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT-EGF conjugates, at a concentration of 85 µg ml(-1), to the PANC-1 cell surfaces was significant in the first 30 min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNT-EGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone.

Cytotoxicity and biological effects of functional nanomaterials delivered to various cell lines.

Functional nanomaterials that included gold, silver nanoparticles and single wall carbon nanotubes were delivered to two cell lines (MLO-Y4 osteocytic cells and HeLa cervical cancer cells) in various concentrations. The cells were found to uptake the nanomaterials in a relatively short time, a process that significantly affected the shape and the size of the cells. The percentage of cellular death, due to the delivery of these nanomaterials, was found to be the highest for carbon nanotubes and increased gradually with the concentration of these nanostructures. Moreover, when the nanomaterials were delivered to the cells combined with commonly used chemotherapeutic agents such as etoposide or dexamethasone, the number of the cells that died increased significantly (100-300%) as compared with the case when only the nanomaterials or the chemotherapeutic agents were delivered. The experimental results were confirmed by Caspase 3 studies, indicating a strong interaction between the nanomaterials used in this study and the protein structure of the cells, which allowed a more effective action of the apoptotic agents. These findings could be the foundation of a new class of cancer therapies that are composed of both chemotherapeutic agents and nanomaterials.

Large-scale graphene production by RF-cCVD method.

In this work, we report a low-cost facile method for the production of few-layer graphene sheets in large quantities through radio-frequency chemical vapor deposition.

Quantification of cellular associated graphene and induced surface receptor responses.

The use of graphene for biomedical and other applications involving humans is growing and shows practical promise. However, quantifying the graphitic nanomaterials that interact with cells and assessing any corresponding cellular response is extremely challenging. Here, we report an effective approach to quantify graphene interacting with single cells that utilizes combined multimodal-Raman and photoacoustic spectroscopy. This approach correlates the spectroscopic signature of graphene with the measurement of its mass using a quartz crystal microbalance resonator. Using this technique, we demonstrate single cell noninvasive quantification and multidimensional mapping of graphene with a detection limit of as low as 200 femtograms. Our investigation also revealed previously unseen graphene-induced changes in surface receptor expression in dendritic cells of the immune system. This tool integrates high-sensitivity real-time detection and monitoring of nanoscale materials inside single cells with the measurement of induced simultaneous biological cell responses, providing a powerful method to study the impact of nanomaterials on living systems and as a result, the toxicology of nanoscale materials.

CO2 enhanced carbon nanotube synthesis from pyrolysis of hydrocarbons.

We report on the role of CO(2) in improving carbon nanotube yield and crystallinity from catalytic chemical vapor deposition of hydrocarbons.

Effects of the Fe-Co interaction on the growth of multiwall carbon nanotubes.

The influences of active species Fe-Co composition on the growth of carbon nanotubes (CNTs) were systemically investigated. CNTs were grown from the pyrolytic decomposition of C(2)H(2) over Fe-Co/CaCO(3) catalysts by radio frequency chemical vapor deposition (CVD). The catalyst stoichiometry was found to strongly influence the carbon deposition rate as well as the nanotube crystallinity characteristics. Compared to the CNTs synthesized over the Co/CaCO(3) catalyst, those produced by Fe-containing catalysts have less amorphous carbon. The maximum yield of high-quality CNTs was achieved at the Fe/Co atomic ratio of 2:1 due to a suitable concentration of benzene generated from acetylene CVD on such catalytic system. Fe and Co can form alloy and therefore the d-electron interaction between Fe and Co was believed to play an important role in the CNT growth.

Direct electrochemical oxidation of S-captopril using gold electrodes modified with graphene-AuAg nanocomposites.

In this paper, we present a novel approach for the electrochemical detection of S-captopril based on graphene AuAg nanostructures used to modify an Au electrode. Multi-layer graphene (Gr) sheets decorated with embedded bimetallic AuAg nanoparticles were successfully synthesized catalytically with methane as the carbon source. The two catalytic systems contained 1.0 wt% Ag and 1.0 wt% Au, while the second had a larger concentration of metals (1.5 wt% Ag and 1.5 wt% Au) and was used for the synthesis of the Gr-AuAg-1 and Gr-AuAg-1.5 multicomponent samples. High-resolution transmission electron microscopy analysis indicated the presence of graphene flakes that had regular shapes (square or rectangular) and dimensions in the tens to hundreds of nanometers. We found that the size of the embedded AuAg nanoparticles varied between 5 and 100 nm, with the majority being smaller than 20 nm. Advanced scanning transmission electron microscopy studies indicated a bimetallic characteristic of the metallic clusters. The resulting Gr-AuAg-1 and Gr-AuAg-1.5 samples were used to modify the surface of commonly used Au substrates and subsequently employed for the direct electrochemical oxidation of S-captopril. By comparing the differential pulse voltammograms recorded with the two modified electrodes at various concentrations of captopril, the peak current was determined to be well-defined, even at relatively low concentration (10(-5) M), for the Au/Gr-AuAg-1.5 electrode. In contrast, the signals recorded with the Au/Gr-AuAg-1 electrode were poorly defined within a 5×10(-6) to 5×10(-3) M concentration range, and many of them overlapped with the background. Such composite materials could find significant applications in nanotechnology, sensing, or nanomedicine.

Few-layer graphene sheets with embedded gold nanoparticles for electrochemical analysis of adenine.

This work describes the synthesis of few-layer graphene sheets embedded with various amounts of gold nanoparticles (Gr-Au-x) over an Aux/MgO catalytic system (where × = 1, 2, or 3 wt%). The sheet-like morphology of the Gr-Au-x nanostructures was confirmed by transmission electron microscopy and high resolution transmission electron microscopy, which also demonstrated that the number of layers within the sheets varied from two to seven. The sample with the highest percentage of gold nanoparticles embedded within the graphitic layers (Gr-Au-3) showed the highest degree of crystallinity. This distinct feature, along with the large number of edge-planes seen in high resolution transmission electron microscopic images, has a crucial effect on the electrocatalytic properties of this material. The reaction yields (40%-50%) and the final purity (96%-98%) of the Gr-Au-x composites were obtained by thermogravimetric analysis. The Gr-Au-x composites were used to modify platinum substrates and subsequently to detect adenine, one of the DNA bases. For the bare electrode, no oxidation signal was recorded. In contrast, all of the modified electrodes showed a strong electrocatalytic effect, and a clear peak for adenine oxidation was recorded at approximately +1.05 V. The highest increase in the electrochemical signal was obtained using a platinum/Gr-Au-3-modified electrode. In addition, this modified electrode had an exchange current density (I(0), obtained from the Tafel plot) one order of magnitude higher than that of the bare platinum electrode, which also confirmed that the transfer of electrons took place more readily at the Gr-Au-3-modified electrode.

Multifunctional magnetic nanoparticles for synergistic enhancement of cancer treatment by combinatorial radio frequency thermolysis and drug delivery.

Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with controlled sizes ranging from 7 to 9 nm. The additional loading of two anti-cancer drugs, doxorubicin and erlotinib, was achieved through - stacking onto the carbon shells. Controlled release of the drugs was successfully triggered by radio frequency (RF) heating or pH variation. Based on the experimental results, C/Fe MNPs act as heat-inducing agents and are able to thermally destroy cancer cells when RF is applied. It was found that the combination of anti-cancer drugs (in particular a low dose of doxorubicin) and RF treatment demonstrates a synergistic effect in inducing cell death in pancreatic cancer cells. Our findings demonstrate that MNPs can be used as highly efficient multimodal nanocarrier agents for an integrated approach to cancer treatment involving triggered delivery of antineoplastic drugs and RF-induced thermal therapy.

Catalytic conversion of graphene into carbon nanotubes via gold nanoclusters at low temperatures.

Here, we present the catalytic conversion of graphene layers into carbon nanotubes (CNTs), in the presence of Au nanoparticles (AuNPs) without the need for an additional carbon source. We have demonstrated that this catalytic process takes place at temperatures as low as 500 °C. No other oxide supports decorated with AuNPs were found to grow CNTs at this temperature. These findings highlight the high activity of graphene when used as a support for catalytic reactions.

Carbon-covered magnetic nanomaterials and their application for the thermolysis of cancer cells.

Three types of graphitic shelled-magnetic core (Fe, Fe/Co, and Co) nanoparticles (named as C-Fe, C-Fe/Co, and C-Co NPs) were synthesized by radio frequency-catalytic chemical vapor deposition (RF-cCVD). X-ray diffraction and X-ray photoelectron spectroscopy analysis revealed that the cores inside the carbon shells of these NPs were preserved in their metallic states. Fluorescence microscopy images indicated effective penetrations of the NPs through the cellular membranes of cultured cancer HeLa cells, both inside the cytoplasm and the nucleus. Low RF radiation of 350 kHz induced localized heating of the magnetic NPs, which triggered cell death. Apoptosis inducement was found to be dependent on the RF irradiation time and NP concentration. It was showed that the Fe-C NPs had a much higher ability of killing the cancer cells (over 99%) compared with the other types of NPs (C-Co or C-Fe/Co), even at a very low concentration of 0.83 microg/mL. The localized heating of NPs inside the cancer cells comes from the hysteresis heating and resistive heating through eddy currents generated under the RF radiation. The RF thermal ablation properties of the magnetic NPs were correlated with the analysis provided by a superconducting quantum interference device (SQUID).

Investigation of carbon nanofibers as support for bioactive substances.

In this paper we have studied the adsorption properties of various bio-active systems onto the surface of carbon nanofibers (CNF) synthesized by chemical vapor deposition (CVD). Amino acids (alanine, aspartic acid, glutamic acid) and glucose oxidase (GOx) were adsorbed on CNF and the results were compared with those obtained when activated carbon (AC) was used as support. CNF and AC properties (hydrophilic or hydrophobic properties) were characterized by the pH value, the concentration of acidic/basic sites and by naphthalene adsorption. CNF with immobilized GOx was additionally investigated as a highly sensitive glucose biosensor. An amperometric method was used in an original manner to detect the changes in the specific activity of GOx, immobilized longer time on CNF. The method demonstrates that not the whole enzyme adsorbed onto CNF can catalyze the oxidation of glucose from the solution.

Light-harvesting using high density p-type single wall carbon nanotube/n-type silicon heterojunctions.

Photovoltaic conversion was achieved from high-density p-n heterojunctions between single-wall carbon nanotubes (SWNTs) and n-type crystalline silicon produced with a simple airbrushing technique. The semitransparent SWNT network coating on n-type silicon substrate forms p-n heterojunctions and exhibits rectifying behavior. Under illumination the numerous heterojunctions formed between substrate generate electron-hole pairs, which are then split and transported through SWNTs (holes) and n-Si (electrons), respectively. The nanotubes serve as both photogeneration sites and a charge carriers collecting and transport layer. Chemical modification by thionyl chloride of the SWNT coating films was found to significantly increase the conversion efficiency by more than 50% through adjusting the Fermi level and increasing the carrier concentration and mobility. Initial tests have shown a power conversion efficiency of above 4%, proving that SOCl(2) treated-SWNT/n-Si configuration is suitable for light-harvesting at relatively low cost.

Synergistic enhancement of cancer therapy using a combination of carbon nanotubes and anti-tumor drug.

AIM: In previous pharmacological applications, single-wall carbon nanotubes (CNTs) have primarily been explored as potential drug carriers and delivery vehicles. Here, we investigate and demonstrate for the first time, that CNTs can be considered as anti-tumor agents and, when in combination with conventional drugs, can significantly enhance their chemotherapeutic effects. METHOD & MATERIALS: HeLa and human Panc1 cancer cells were treated with CNTs (24 h, 10 and 20 microg/ml), etoposide (6 h, 75 x 10(-6) M) and their combination. The cell viability was controlled by flow cytometry, caspase-3 assay and trypan blue dye. RESULTS: A highly increased anti-tumor activity of the combination of etoposide and CNTs against cancer cells, compared with the administration of etoposide and CNTs alone, is reported. Data provided by viability assays suggest a strong interaction between CNTs and the cellular structures, thereby improving the effectiveness of conventional chemotherapeutic agents. CONCLUSION: We believe this finding could lead to the development of new cancer therapies by carefully selecting the cytostatic drugs and nanostructural materials that, in combination, may provide synergistic curative rates.

Comparative study on different carbon nanotube materials in terms of transparent conductive coatings.

We compared conductive transparent carbon nanotube coatings on glass substrates made of differently produced single-wall (SWNT), double-wall, and multiwall carbon nanotubes. The airbrushing approach and the vacuum filtration method were utilized for the fabrication of carbon nanotube films. The optoelectronic performance of the carbon nanotube film was found to strongly depend on many effects including the ratio of metallic-to-semiconducting tubes, dispersion, length, diameter, chirality, wall number, structural defects, and the properties of substrates. The electronic transportability and optical properties of the SWNT network can be significantly altered by chemical doping with thionyl chloride. Hall effect measurements revealed that all of these thin carbon nanotube films are of p-type probably due to the acid reflux-based purification and atmospheric impurities. The competition between variable-range hoping and fluctuation-assisted tunneling in the functionized carbon nanotube system could lead to a crossover behavior in the temperature dependence of the network resistance.