OVERVIEW ON THE MAJOR RESEARCH ACTIVITIES ON CARBON NANOTUBES BEING DONE IN AMERICA, EUROPE AND ASIA - Carbon Nanotubes: From Bench Chemistry to Promising Biomedical Applications - page 296

of electrical cellular interfacing. Nanostructures offer the advantage of
translocating across the blood-brain barrier (BBB) and eventually migrating
along axons and dendrites and even crossing synapses. 182 Aside from
establishing an electronic communication link with neural tissue, they seem
to be particularly suitable for developing neuronal electrodes (NEs) to be
applied in case of devastating diseases (e.g., Parkinson's and Alzheimer's
diseases, sclerosis and paralysis). In this context, CNTs are excellent candidates
for interfacing with neural systems for the development of biocompatible,
durable and robust neuroprosthetic devices. This is because they present
extraordinary strength, toughness, electrical conductivity and high surface
area. The inluence of CNTs in neuronal living networks is developed in chapter
7. Quite recently (in 2000) CNTs were promoted as substrates for neuronal
growth, 183 since the neuronal bodies were able to adhere to CNTs' surface
with neurites extending through the bed of CNTs and developing into many
branches. The neurons remained alive on CNTs for at least 11 days, stimulating
other scientists to investigate the role of CNTs in the central nervous system
(CNS). In fact, Prato's group demonstrated the spontaneous post-synaptic
currents (PSCs) from a single neuron associated with CNTs, thus indicating
functional synapse formation. 184 The sample used consisted of CNTs initially
functionalised and subsequently subjected to thermal treatment in order
to recover unfunctionalised and puriied tubes. They provided an eficient
substrate for hippocampal cell growth with dimensions comparable with the
controls (CNT-free neurones) and promoted a signiicant increase in brain
network operation. An additional interesting aspect is that, despite being
highly electrically conductive, pristine CNTs can be chemically modiied with
different biomolecules while maintaining their intrinsic properties. To that
purpose, Prato's group has explored the functionalisation of multi-walled
carbon nanotubes ( f -MWCNTs) with cell adhesion peptides, to be potentially
delivered at the site of nerve injury to promote local tissue repair. 185 In these
experiments, MWCNTs were preferred because of their wider external
surface. They underwent both oxidation (to cut them into smaller tubes)
and 1,3-dipolar cycloaddition of azomethine ylides ( Fig. 9.30) , after which
the free amino group was coupled with the maleimido function and then
the selected peptides. The irst sequence corresponded to Gly-Arg-Gly-Asp-
Ser-Pro (GRGDSP, Pep 1), which is a ibronectin-derived peptide capable of
increasing integrin-mediated cell adhesion and spreading via the cell-binding
domain RGD residues. Coating surfaces with RGD-based sequences have
shown to promote not only cell adhesion but also neurite outgrowth. 186 The
second selected sequence corresponded to Ile-Lys-Val-Ala-Val (IKVAV, Pep 2)
contained in laminin.
With the aim to design peptide-MWCNT conjugates for interacting with
neuronal cells, hippocampal neurons were treated with soluble peptide-
MWCNTs 5 and 6, with the control peptides alone, and with MWCNTs 3