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Abstract: The use of controlled electric fields to facilitate cell permeabilisation for enhanced cellular uptake of molecules is well established. The main limitation to the application of this technology in clinical practice is the requirements of high voltages which cause significant cell death in the target tissue. This paper presents a new modality for cell electro-permeabilisation based on the use of carbon nanotubes (CNTs) and external static electric fields. An explanation of the results based on the dielectric response of multiwall CNTs (MWCNTs) to these electric fields is proposed. The experimental data obtained indicate that this method of CNT-enhanced electro-permeabilisation provides an effective means of lowering the electric field voltage required for repairable cell electro-permeabilisation to below 50V/cm and with an efficiency exceeding 80%. [Copyright &y& Elsevier]

Abstract: There are conflicting data concerning the safety and biocompatibility of carbon nanotubes (CNTs). In some reports CNTs have been used for gene delivery without significant toxicity, whereas in others various cytotoxic effects were observed, including induction of intracellular reactive oxygen species (ROS), DNA damage, and apoptosis. Although it is clear that CNT production methods, purity, and functionalization treatments impact on biocompatibility, most of the published reports lack detailed characterization of the CNT samples used. We investigated the effect of various physicochemical features of multiwalled carbon nanotubes (MWCNTs) on toxicity and biocompatibility with cultured human neuroblastoma cells by using MTT, WST-1, Hoechst, and oxidative stress assays. In vitro experiments confirm that after 3 days of incubation with three different types of CNTs dispersed in Pluronic F127 solution, 0.01% cell viability is not affected and apoptosis and ROS are not induced in the SH-SY5Y cells. With prolonged cultures and continued propagation in the presence of MWCNTs, the loss of cell viability was minimal for pure MWCNTs (99% purity), but cell proliferation decreased significantly for 97% purity MWCNTs and acid-treated MWCNTs (97% purity, surface oxidation 8%); no intracellular ROS were detected. When the concentration of CNTs increases, purity and surface oxidation seem to affect cell viability (ED25 is 48, 34.4, and 18.4 μg/mL, respectively, for 99% purity MWCNTs, 97% purity MWCNTs, and acid-treated 97% purity MWCNTs. Our results indicate that concentrations of 5–10 μg/mL MWCNTs seem ideal for studies on the design and development of artificial MWCNT nanovectors for gene and drug therapy against cancer. From the Clinical Editor: With prolonged cultures, loss of cell viability was minimal for preparations with 99% purity, but significant adverse effects were detected with 97% purity and with acid-treated preparations. A concentrations of 5–10 μg/mL of MWCNTs seems ideal for gene and drug therapy against cancer. [Copyright &y& Elsevier]

In this article, a carbon nanotube (CNT) array-based system combined with a polymer thin film is proposed as an effective drug release device directly at cellular level. The polymeric film embedded in the CNT array is described and characterized in terms of release kinetics, while in vitro assays on PC12 cell line have been performed in order to assess the efficiency and functionality of the entrapped agent (neural growth factor, NGF). PC12 cell differentiation, following incubation on the CNT array embedding the alginate delivery film, demonstrated the effectiveness of the proposed solution. The achieved results indicate that polymeric technology could be efficiently embedded in CNT array acting as drug delivery system at cellular level. The implication of this study opens several perspectives in particular in the field of neurointerfaces, combining several functions into a single platform. [ABSTRACT FROM AUTHOR]

Abstract: Carbon nanotubes (CNTs) are nanodevices with important potential applications in biomedicine such as drug and gene delivery. Brain diseases with no current therapy could be candidates for CNT-based therapies. Little is known about toxicity of CNTs and of their dispersion factors in the brain. Here we show that multiwall CNTs (MWCNTs) coated with Pluronic F127 (PF127) surfactant can be injected in the mouse cerebral cortex without causing degeneration of the neurons surrounding the site of injection. We also show that, contrary to previous reports on lack of PF127 toxicity on cultured cell lines, concentrations of PF127 as low as 0.01% can induce apoptosis of mouse primary cortical neurons in vitro within 24 hours. However, the presence of MWCNTs can avoid PF127-induced apoptosis. These results suggest that PF127-coated MWCNTs do not induce apoptosis of cortical neurons. Moreover, the presence of MWCNTs can reduce PF127 toxicity. [Copyright &y& Elsevier]

Because mass-produced carbon nanotubes (CNTs) are strongly aggregated and highly hydrophobic, processes to make them water soluble are required for biological applications. Suspensions in surfactant solutions are often employed. Among these, Pluronic F127 appear to be highly biocompatible if used at low concentrations. Starting from these results, this work involves a systematic study to clarify the dispersion behaviour of CNTs in Pluronic F127. The results suggest a two-step process: first, the bundles disaggregate, kinetically driven by the energy supplied to the system; second, they disperse (surfactant adsorption), thermodynamically driven by the surfactant concentration. The dispersion reaction data are well fitted by a first-order kinetics reaction. By performing a pretreatment step, consisting of stirring at 70°C, the achieved concentration of CNTs in solution is twice that of the traditional process. The proposed procedure provides an optimal compromise between a low Pluronic concentration and a high CNT concentration. [ABSTRACT FROM AUTHOR]

Abstract: Carbon nanotubes (CNTs) are widely used for biomedical applications as intracellular transporters of (bio)molecules, due to their high propensity to cross cell membranes. However, there is a clear discrepancy in the literature about their uptake mechanism, which should be related to the differences existing in the nanotube materials, as well as the experimental procedures. Despite the fact that there are some studies on the influence of the CNT surface chemistry, the role of the properties of non-functionalized CNTs in cellular uptake has not been much investigated to a great extent. In this work, different kinds of multi-wall CNTs (MWCNTs) are produced and fully characterized, in terms of diameter, length, metal impurity, carbon soot and surface chemistry. These MWCNT samples are tested in vitro, and the cellular uptake is indirectly evaluated by using standard fluorescent probes and confirmed by TEM images. Our assays demonstrate that nanotube length clearly influences their uptake and shorter (sub-1μm) MWCNTs are easier to be internalized through an energy-independent pathway. The results of this investigation may be useful for the design of promising CNT-based vectors for cell therapy. [Copyright &y& Elsevier]

Summary: Boron nitride nanotubes are structural analogues of carbon nanotubes in nature: alternating B and N atoms entirely substitute for C atoms in a graphitic like sheet with almost no change in atomic spacing. Despite their unique physical and chemical properties, their use has not yet been exploited in the nanomedicine field. In this Opinion, the authors briefly summarize the results of their studies on the interactions between boron nitride nanotubes and living cells and outline future and realistic applications for their use in the biomedical field. [Copyright &y& Elsevier]

We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants. The nanohybrid strongly enhances the cytotoxic effect of (+)-catechin. At a concentration of (+)-catechin 50 μg/ml, the nanohybrid inhibited the ability of melanoma cells to proliferate (100% increase of cell doubling time and severe impairment in zebrafish xenotransplants), to migrate (totally inhibition in vitro and 50% reduction of cell motility in zebrafish xenotransplants) and to induce neo-angiogenesis (100% inhibition in zebrafish xenotransplants). Conversely, the free (+)-catechin and carrier (CNT:gel) had no statistically significant effects over the control, at any concentration tested. Our results suggest that the use of the nanohybrid, able to improve the therapeutic efficacy of the catechins, could represent a successful strategy for a future clinical translation. [ABSTRACT FROM AUTHOR]