BIOMEDICAL APPLICATIONS II: INFLUENCE OF CARBON NANOTUBES IN CANCER THERAPY - Carbon Nanotubes: From Bench Chemistry to Promising Biomedical Applications - page 62

It is also necessary to mention some adverse effects on genetic materials
reported for CNTs. The genome expression of human skin ibroblast cells,
exposed to MWCNTs, was analysed. At cytotoxic doses, the CNTs induced
cell cycle arrest and increased apoptosis/necrosis. Expression array analysis
indicated that some cellular pathways were altered with the activation of
genes involved in cellular transport, metabolism, cell cycle regulation and
stress response, inducing the expression of genes indicative of a strong
immune and inlammatory response. 48 Moreover, MWCNTs have been proved
to induce apoptosis in embryonic stem cells and to cause a twofold increase
in the mutation frequency, damaging DNA. 49 One possible explanation,
suggested by the authors, is the production of reactive oxygen species in
these conditions, but this theory can be considered controversial taking into
account that CNTs are considered to act as free radical scavengers. 50,51

3.5 CARBON NANOTUBES IN RADIOTHERAPY

Up to now the main use of radioisotopes linked to CNTs inds application in
imaging studies, to determine the biodistribution of the derivatives following
the radioisotope traces. Many different approaches in this sense have been
reported using variously functionalised CNTs. In the non-covalent strategy
adopted by Liu et al ., CNTs were wrapped with PEG chains bearing 1,4,7,10-
tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to chelate 64 Cu, a
β

+ -emitting radionuclide used in positron emitting tomography (PET). 52 The
covalent approach has been used by McDevitt et al. and Singh et al. 53,54 In both
cases the 1,3-dipolar cycloaddition of azomethine ylides as functiolisation
methodology and 111 In as γ -emitting radiotracer were employed. McDevitt
et al. reported the preparation of an SWCNT derivative using DOTA as the
chelating agent. Biodistribution studies showed a signiicative accumulation
in the kidney, spleen and liver. In in vivo experiments on a murine model
of disseminated human lymphoma, there was a selective targeting of the
tumour when a speciic monoclonal antibody was conjugated (compound
16 in Fig. 3.11) , demonstrating the eficacy of this approach. 53 Singh et al .,
instead, presented CNTs bearing diethylene triamine pentaacetic acid (DTPA)
linked to the amine residues, since DTPA is a known chelating agent for
111 In (compound 17 ). Also in this case the derivative was used to perform
biodistribution studies, and it emerged that CNTs were mainly excreted by
urine and that after intravenous administration their blood circulation half-
life was about 3.5 hours.