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 292

of siRNA, the researchers have comparatively studied the in vivo cytotoxic
effects of complexes including a toxic siRNA sequence (siTOX) with either
functionalised MWCNTs or cationic liposomes (DOTAP:Chol). 173 Speciicity
for all human tumour cell lines was evidenced by the dramatic enhancement
of cytotoxicity compared with that obtained for the panel of murine cells.
In addition, Calu 6 (human lung carcinoma) cells were chosen to prepare
human tumour xenografts and comparatively study the in vivo cytotoxic
activity of siTOX delivered by either liposomes or MWCNT-NH 3 + . Results
showed that the liposome:siTOX complexes had maximum activity at 72
hours post-transfection, while the MWCNT-NH 3 + :siRNA complexes reached
their optimum after 24 hours, suggesting a faster translocation through the
plasma membrane in comparison with liposomes. A MWCNT-NH 3 + :siRNA at
8:1 mass ratio was used, demonstrating that mice prolonged survival only
for the MWCNT-NH 3 + :siTOX 50 days after Calu 6 xenograft implantation, with
a much higher potency compared with cationic liposomes. Overall, siTOX
delivery via cationic MWCNT-NH 3 + was successful at triggering an apoptotic
cascade with extensive necrosis of the human tumour cells and a tumour
collapse from the inside of the cancerous mass.
In terms of drug delivery, the authors recently described a previously
unreported supramolecular complex formed by the non-covalent
functionalisation of MWCNTs and the drug doxorubicin for cancer
therapy. 174 The advantage of using doxorubicin is that this anthracycline
is a luorescent molecule in view of its chromophore composed of three
aromatic hydroxyanthraquinone rings, and hence it can be used as a drug
as well as a luorescent tag to monitor its supramolecular interaction with
MWCNTs. It was observed that CNTs were able to quench doxorubicin to an
extent proportional to their concentration, most probably due to the π - π
stacking interaction between the aromatic chromophore groups and the
CNT backbone. Importantly, mitochondrial reductase activity (MTT) assays
of these supramolecular complexes showed enhancement in cytotoxic
capability of the drug, but tubes alone did not affect cell viability. These data
also suggested that MWCNTs can mediate the delivery of doxorubicin and
hence improve the cellular uptake of the drug.
The group has also reported a compelling mechanism by which CNTs
seem to be excreted through the normal renal pathway. 175 In previous studies,
it was seen that radio-labelled CNTs were found in the urine samples after
intravenous (tail vein) administration in mice. 176 In addition, intravenously
administered MWCNTs, functionalised with the alkylating agent
diethylenetriaminepentaacetic acid (DTPA) and radio-labelled with indium
[ 111 In], were dynamically tracked in vivo using a micro-single photon emission
tomography scanner. 177 Imaging showed that nanotubes entered the systemic
blood circulation and within 5 minutes began to permeate through the renal