In vivo degradation of functionalized carbon nanotubes after stereotactic administration in the brain cortex (original) (raw)
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PLoS ONE, 2013
The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH 3 + ) and amino-functionalized MWNT (MWNT-NH 3 + ). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications.
Journal of Controlled Release, 2015
Earlier studies proved the success of using chemically functionalised multi-walled carbon nanotubes (f-MWNTs) as nanocarriers to the brain. Little insight into the kinetics of brain distribution of f-MWNTs in vivo has been reported. This study employed a wide range of qualitative and quantitative techniques with the aim of shedding the light on f-MWNT's brain distribution following intravenous injection. γ-Scintigraphy quantified the uptake of studied radiolabelled f-MWNT in the whole brain parenchyma and capillaries while 3D-single photon emission computed tomography/computed tomography imaging and autoradiography illustrated spatial distribution within various brain regions. Raman and multiphoton luminescence together with transmission electron microscopy confirmed the presence of intact f-MWNT in mouse brain, in a label-free manner. The results evidenced the presence of f-MWNT in mice brain parenchyma, in addition to brain endothelium. Such information on the rate and extent of regional and cellular brain distribution is needed before further implementation into neurological therapeutics can be made.
Carbon nanotubes (CNTs) are gradually emerging as a new option for possible use in neural prosthesis, drug delivery, cancer treatment, bioengineering, gene therapy and regeneration therapy. With an increase in the development and application of CNT-based medicinal products, the potential hazards of CNTs to biological systems are getting greater public attention. A lack of toxicity information and safety standards has hampered possible applications of the CNT-based products in humans and animals. Since many CNT-based products are designed for the central nervous systems (CNS) applications (neural pros-thesis, drug delivery and regeneration therapy), it is important to understand the danger these nanotubes may pose to the CNS. Therefore, the aims of article is to review the adverse effects of different forms of CNTs on the CNS, the role of protein corona in CNTs' toxicity, the challenges the adverse effects pose in applications of the CNT-based products, and possible mechanism for the evolution of CNTs's neurotoxicity. The information presented in this review will be useful in designing more effective and safer CNT-based products.
Pluronic-coated carbon nanotubes do not induce degeneration of cortical neurons in vivo and in vitro
Nanomedicine: Nanotechnology, Biology and Medicine, 2009
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.
Carbon nanotubes exert excitatory electrophysiological effects on rat brain slices
Frontiers in Systems Neuroscience, 2009
carbon nanotubes are promising new tools in biomedicine but they may have yet some unknown influences on the organism. in the present study, the acute effect of solubilized, multi-walled carbon nanotubes (MWCnts) on basic neuronal functions was examined. rat brain slices were treated in vitro with nanotube-containing colloid solutions at concentrations of 100-800 µg/ml and evoked field potentials were recorded from the somatosensory cortex and hippocampus. basic excitability of the treated slices was characterized by the amplitude of field excitatory postsynaptic potentials (fePsPs) and population spikes. experimental results indicated significantly higher excitability of treated samples than that of controls. Multiple components in evoked potentials were observed, which is in accordance with the increased excitability of investigated brain areas. tests of short-and long-term plasticity were also performed, which revealed no difference between control and treated slices. experimental results suggest an interaction between nanotubes and brain tissue. MWCnts seem to act on the basic membrane potential of neurons by changing membrane properties or via a mechanism linked to voltage-gated ion channels, rather than influencing specific synaptic transmission. Further investigation is needed to clarify the nature of interactions between nanotubes and brain tissue.
Carbon Nanotubes and Neurons:Nanotechnology Application to the Nervous System
2010
Nella mia giovinezza ho navigato lungo le coste dalmate. Isolotti a fior d'onda emergevano, ove raro un uccello sostava intento a prede, coperti d'alghe, scivolosi, al sole belli come smeraldi. Quando l'alta marea e la notte li annullava, vele sottovento sbandavano più al largo, per fuggirne l'insidia. Oggi il mio regno è quella terra di nessuno. Il porto accende ad altri i suoi lumi; me al largo sospinge ancora il non domato spirito, e della vita il doloroso amore.
Carbon, 2015
Pristine (as prepared) carbon nanotube (CNT) based substrates have been widely used to grow and interface neurons in culture. Nerve cells normally differentiate on CNTs and the synaptic networks, newly formed at the interface with this material, usually show an improved robustness in signal transfer. However manipulation of pristine CNTs is often prevented by their low dispersibility and tendency to aggregate in most solvents. This issue can be at least partially solved by adding solubilizing groups to the surface of CNT, which also helps improving their biocompatibility. It becomes therefore of crucial importance to determine whether chemically manipulated CNTs may maintain their performance in improving nerve signaling. Here we study and compare the impact in vitro on neuronal signaling of two classes of chemically modified multiwalled CNTs in reference to pristine CNTs, which are known to be a substrate able to boost neuronal growth and communication. We found that the extent of functionalization and the nature of the functional groups on MWNT sidewalls affect the conductivity and the biological effects of the final derivatives. This information is important for the future design of biointegrated devices.
Carbon nanotubes exert basic excitatory enhancement in rat brain slices
Acta Biologica Hungarica, 2013
carbon nanotubes are promising new tools in biomedicine but they may have yet some unknown influences on the organism. in the present study, the acute effect of solubilized, multi-walled carbon nanotubes (MWCnts) on basic neuronal functions was examined. rat brain slices were treated in vitro with nanotube-containing colloid solutions at concentrations of 100-800 µg/ml and evoked field potentials were recorded from the somatosensory cortex and hippocampus. basic excitability of the treated slices was characterized by the amplitude of field excitatory postsynaptic potentials (fePsPs) and population spikes. experimental results indicated significantly higher excitability of treated samples than that of controls. Multiple components in evoked potentials were observed, which is in accordance with the increased excitability of investigated brain areas. tests of short-and long-term plasticity were also performed, which revealed no difference between control and treated slices. experimental results suggest an interaction between nanotubes and brain tissue. MWCnts seem to act on the basic membrane potential of neurons by changing membrane properties or via a mechanism linked to voltage-gated ion channels, rather than influencing specific synaptic transmission. Further investigation is needed to clarify the nature of interactions between nanotubes and brain tissue.