BIOMEDICAL APPLICATIONS II: INFLUENCE OF CARBON NANOTUBES IN CANCER THERAPY - Carbon Nanotubes: From Bench Chemistry to Promising Biomedical Applications - page 59

inhibit cell growth. This activity was conserved in both in vitro experiments
(performed on LLC, TC1 and1H8 cell lines) and in vivo . 39 This approach can be
really interesting considering the possibility of exploiting the two different
actions of CNTs as oligonucleotide vectors and i-motif stabilisers.
Liu et al . used non-covalently functionalised SWCNTs bearing positive
charges to deliver siRNA into HeLa cells, 40 T cells and primary cells. 41 The
oligonucleotide was attached by disulphide bonds to phospholipidic-
PEG chains used to wrap CNTs (compound 13 , Fig. 3.8). Depending on the
length of the PEG chain, the delivery resulted in being differently effective,
corresponding to the differences in eficiency for the internalisation of the
nanotubes into cells. The presence of long PEG chain (PEG 5400 ) gave the worst
results, while the use of PEG 2000 was successful, as demonstrated using Raman
spectroscopy to localise the presence of the SWCNTs inside cells.

13 14

= phospholipid-PEG = PEI

= siRNA = antisense oligonucleotid

= CdTe quantum dot

Figure 3.8 Structures of compounds 13 and 14 .

As previously described (see Section 3.3 ) Yang et al. reported the use of
phospholipid-PEG chains derivatised with folic acid to deliver a luorescently
labelled dsDNA, obtaining a selective internalisation in tumour cells
overexpressing folate receptors. 20
Also Jia et al. reported the use of CNTs to deliver into cells antisense
oligonucleotides able to hybridise mRNA and consequently inhibit protein
expression, which is a mechanism of interest in cancer treatment. Oxidised
MWCNTs were used to complex polyethyenimine (PEI), which can interact
with an antisense sequence by means of electrostatic forces. In this case the
oligonucleotide was linked to the cadmium telluride (CdTe) quantum dot.
This luorescent marker was used to follow the cellular traficking of the
complex, demonstrating that, using derivative 14 , the uptake took place by
endocytosis and was eficient. Moreover, the system exerted the expected
anticancer activity. 42