Chloroquine-enhanced gene delivery mediated by carbon nanotubes

Polyethyleneimine-coated double-walled carbon nanotubes (DWCNTs) were used for dual gene and drug delivery, after loading the DWCNTs with the drug chloroquine, a lysosomotropic compound that is able to promote escape from the lysosomal compartment. Different forms of functionalization of the DWCNTs were examined in order to optimize this system. They included the testing of different treatments on DWCNTs to optimize the loading and delivery of chloroquine and the selection of a cationic polymer for coating the DWCNTs for optimum DNA binding and delivery. An acid oxidation treatment of DWCNTs was selected for optimum chloroquine loading together with polyethyleneimine as optimum cationic coating agent for plasmid DNA binding. Optimization of the conditions for choroquine-enhanced gene delivery were developed using luciferase expression as a model system. We have demonstrated that chloroquine-loading increases the ability of polyethyleneimine-coated DWCNTs to deliver functional nucleic acid to human cells. Cell viability tests have shown no cytotoxicity of the functionalized DWCNTs at the concentrations needed for optimum gene delivery. These results support the potential applications of this methodology in gene therapy

Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung

With the rapid spread of carbon nanotubes (CNTs) applications, the respiratory toxicity of these compounds has attracted the attention of many scientists. Several studies have reported that after lung administration, CNTs could induce granuloma, fibrosis, or inflammation. By comparison with the mechanisms involved with other toxic particles such as asbestos, this effect could be attributed to an increase of oxidative stress. The aim of the present work was to test this hypothesis in vivo. Mice were intranasally instilled with 1.5 mg/kg of double walled carbon nanotubes (DWCNTs). Six, 24, or 48 h after administration, inflammation and localisation of DWCNTs in lungs were microscopically observed. Local oxidative perturbations were investigated using ESR spin trapping experiments, and systemic inflammation was assessed by measuring the plasma concentration of cytokines TNF-α, IL-1α, IL-1β, IL-6, IGF-1, Leptin, G-CSF, and VEGF. Examination of lungs and the elevation of proinflammatory cytokines in the plasma (Leptin and IL-6 at 6 h) confirmed the induction of an inflammatory reaction. This inflammatory reaction was accompanied by a decrease in the local oxidative stress. This effect could be attributed to the scavenger capability of pure CNTs

Mössbauer Spectroscopy Involved in the Study of the Catalytic Growth of Carbon Nanotubes

Single-walled and thin multiwalled carbon nanotubes are prepared by a catalytic-chemical-vapor-deposition method involving the simultaneous formation of Fe or Co nanometric particles from oxide solid solutions based on Al2O3, MgAl2O4 or MgO. This paper is an overview of the authors’ work on the characterization by Mössbauer spectroscopy used in complement to electron microscopy and specific-surface-area measurements. It is notably attempted to correlate the nature of the different iron phases in the carbon nanotube-metal-oxide powders with the formation mechanisms of the nanotubes. Massive composites and hydrogen storage are proposed as possible applications

Pressure dependence of Raman modes in double wall carbon nanotubes filled with α-Fe.

The preparation of highly anisotropic one-dimensional (1D) structures confined into carbon nanotubes (CNTs) in general is a key objective in CNTs research. In this work, the capillary effect was used to fill double wall carbon nanotubes with iron. The samples are characterized by Mössbauer and Raman spectroscopy, transmission electron microscopy, scanning area electron diffraction, and magnetization. In order to investigate their structural stability and compare it with that of single wall carbon nanotubes (SWNTs), elucidating the differences induced by the inner-outer tube interaction, unpolarized Raman spectra of tangential modes of double wall carbon nanotubes (DWNTs) filled with 1D nanocrystallin α-Fe excited with 514 nm were studied at room temperature and elevated pressure. Up to 16 GPa we find a pressure coefficient for the internal tube of 4.3 cm−1 GPa−1 and for the external tube of 5.5 cm−1 GPa−1. In addition, the tangential band of the external and internal tubes broadens and decreases in amplitude. All findings lead to the conclusion that the outer tube acts as a protection shield for the inner tubes (at least up 16 GPa). Structural phase transitions were not observed in this range of pressure

Design of double-walled carbon nanotubes for biomedical applications

Double-walled carbon nanotubes (DWNTs) prepared by catalytic chemical vapour deposition were functionalized in such a way that they were optimally designed as a nano-vector for the delivery of small interfering RNA (siRNA), which is of great interest for biomedical research and drug development. DWNTs were initially oxidized and coated with a polypeptide (Poly(Lys:Phe)), which was then conjugated to thiol-modified siRNA using a heterobifunctional cross-linker. The obtained oxDWNT–siRNA was characterized by Raman spectroscopy inside and outside a biological environment (mammalian cells). Uptake of the custom designed nanotubes was not associated with detectable biochemical perturbations in cultured cells, but transfection of cells with DWNTs loaded with siRNA targeting the green fluorescent protein (GFP) gene, serving as a model system, as well as with therapeutic siRNA targeting the survivin gene, led to a significant gene silencing effect, and in the latter case a resulting apoptotic effect in cancer cells

Optimising DNA binding to carbon nanotubes by non-covalent methods

The use of carbon nanotubes as a gene delivery system has been extensively studied in recent years owing to its potential advantages over viral vectors. To achieve this goal, carbon nanotubes have to be functionalized to become compatible with aqueous media and to bind the genetic material. To establish the best conditions for plasmid DNA binding, we compare the dispersion properties of single-, double- and multi-walled carbon nanotubes (SWCNTs, DWCNTs and MWCNTs, respectively) functionalized with a variety of surfactants by non-covalent attachment. The DNA binding properties of the functionalized carbon nanotubes were studied and compared by electrophoresis. Furthermore, a bilayer functionalization method for DNA binding on SWCNTs was developed that utilized RNA-wrapping to solubilize the nanotubes and cationic polymers as a bridge between nanotubes and DNA

Pressure screening in the interior of primary shells in double-wall carbon nanotubes

The pressure response of double-wall carbon nanotubes has been investigated by means of Raman spectroscopy up to 10 GPa. The intensity of the radial breathing modes of the outer tubes decreases rapidly but remain observable up to 9 GPa, exhibiting a behavior similar (but less pronounced) to that of single-wall carbon nanotubes, which undergo a shape distortion at higher pressures. In addition, the tangential band of the external tubes broadens and decreases in amplitude. The corresponding Raman features of the internal tubes appear to be considerably less sensitive to pressure. All findings lead to the conclusion that the outer tubes act as a protection shield for the inner tubes whereas the latter increase the structural stability of the outer tubes upon pressure application.Comment: PDF with 15 pages, 3 figures, 1 table; submitted to Physical Review

Strongly correlated properties of the thermoelectric cobalt oxide Ca3Co4O9

We have performed both in-plane resistivity, Hall effect and specific heat measurements on the thermoelectric cobalt oxide Ca$_{3}$Co$_{4}$O$_{9}$. Four distinct transport regimes are found as a function of temperature, corresponding to a low temperature insulating one up to $T_{min}\approx$63 K, a strongly correlated Fermi liquid up to $T^*\approx$140 K, with $\rho=\rho_0+AT^2$ and $A\approx 3.63$ $10^{-2} \mu \Omega cm/K^{2}$, followed by an incoherent metal with $k_Fl\leq 1$ and a high temperature insulator above T$^{**}\approx$510 K . Specific heat Sommerfeld coefficient $\gamma = 93$ mJ/(mol.K$^{2}$) confirms a rather large value of the electronic effective mass and fulfils the Kadowaki-Woods ratio $A/\gamma^2 \approx 0.45$ 10$^{-5}$ $\mu \Omega cm.K^2/(mJ^2mol^{-2})$. Resistivity measurements under pressure reveal a decrease of the Fermi liquid transport coefficient A with an increase of $T^*$ as a function of pressure while the product $A(T^*)^2/a$ remains constant and of order $h/e^2$. Both thermodynamic and transport properties suggest a strong renormalization of the quasiparticles coherence scale of order $T^*$ that seems to govern also thermopower.Comment: 5 pages, 6 figures, accepted for publication in Physical Review

A Study of the Formation of Single- and Double-Walled Carbon Nanotubes by a CVD Method

The reduction in H2/CH4 atmosphere of aluminum-iron oxides produces metal particles small enough to catalyze the formation of single-walled carbon nanotubes. Several experiments have been made using the same temperature profile and changing only the maximum temperature (800-1070 °C). Characterizations of the catalyst materials are performed using notably 57Fe Mo¨ssbauer spectroscopy. Electron microscopy and a macroscopical method are used to characterize the nanotubes. The nature of the iron species (Fe3+, R-Fe, ç-Fe-C, Fe3C) is correlated to their location in the material. The nature of the particles responsible for the high-temperature formation of the nanotubes is probably an Fe-C alloy which is, however, found as Fe3C by postreaction analysis. Increasing the reduction temperature increases the reduction yield and thus favors the formation of surface-metal particles, thus producing more nanotubes. The obtained carbon nanotubes are mostly single-walled and double-walled with an average diameter close to 2.5 nm. Several formation mechanisms are thought to be active. In particular, it is shown that the second wall can grow inside the first one but that subsequent ones are formed outside. It is also possible that under given experimental conditions, the smallest (<2 nm) catalyst particles preferentially produce double-walled rather than single-walled carbon nanotubes

Observation of strong Kondo like features and co-tunnelling in superparamagnetic GdCl3 filled 1D nanomagnets

Filling of carbon nanotubes has been tailored over years to modify the exceptional properties of the 1-dimensional conductor for magnetic property based applications. Hence, such a system exploits the spin and charge property of the electron, analogous to a quantum conductor coupled to magnetic impurities, which poses an interesting scenario for the study of Kondo physics and related phenomena. We report on the electronic transport properties of MWNTs filled with GdCl3 nanomagnets, which clearly show the co-existence of Kondo correlation and cotunelling within the superparamagnetic limit. The Fermi liquid description of the Kondo effect and the interpolation scheme are fitted to the resistance-temperature dependence yielding the onset of the Kondo scattering temperature and a Kondo temperature for this nanocomposite, respectively. Cotunneling of conduction electrons interfering with a Kondo type interaction has been verified from the exponential decay of the intensity of the fano shaped nonzero bias anomalous conductance peaks, which also show strong resonant features observed only in GdCl3 filled MWNT devices. Hence, these features are explained in terms of magnetic coherence and spin-flip effects along with the competition between the Kondo effect and co-tunneling. This study raises a new possibility of tailoring magnetic interactions for spintronic applications in carbon nanotube systems