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 252

side effects. 51,52 As regards the therapeutic eficacy of CNTs conjugated to
doxorubicin (SWCNT-DOX), some in vivo experiments were performed in
SCID mice bearing Raji lymphoma xenograft tumours; 53 these animals were
treated weekly with SWCNT-DOX, free DOX or DOXIL (formulation of DOX
using liposomes). Results showed that the size of the tumours in untreated
controls rapidly increased by 7.5 fold. The SWCNT-DOX (5 mg/kg) treated
group showed a greater inhibition of tumour growth than free DOX at the
equivalent dose, while tumours in mice treated with plain SWCNTs increased
by 6.4 fold, thus indicating that SWCNTs did not affect tumour growth. Finally,
mice treated with DOXIL (5 mg/kg) developed severe toxicity and died.
Therefore, loading of DOX onto SWCNTs increased its therapeutic eficacy
compared with free DOX and decreased side effects of DOXIL. It was also
noticed that such π-stacking interaction was dependent on the nanotube's
diameter, thus suggesting a controlled release rate of molecules from CNTs
on the basis of their diameter. In addition, the concept of “functionalisation
partitioning” of CNTs was anticipated, meaning that it is possible to incorporate
several molecules (e.g., drugs, luorescent dyes and targeting agents) on the
same tubes. As regards this last concept, non-covalent functionalisation was
exploited to tether luorescein and polyethylene glycol moieties onto CNTs
and thus forming a supramolecular complex. 54 Fluorescein was adsorbed
onto the tubes through π -stacking interaction, while PEG chains guaranteed
water solubility.
Interestingly, through optical absorbance and luorescence measurements,
it was observed that the interaction between luorescein and SWCNTs was
pH dependent; in fact it diminished as the pH increased, with concomitant
lower stability at high pHs. It is important to note that luorescence emission
from luorescein adsorbed onto the tubes was quenched to a considerable
extent (~67%), but it was still suficient to act as both luorescent label and
intracellular transporter, as demonstrated by enhanced uptake of SWCNT-
PEG-luorescein by mammalian cells. In this case, Raman analysis was used
to conirm the co-localisation of luorescein and SWCNTs and disprove its
detachment from the tubes.
A further development of this work is provided by the non-covalent
functionalisation of raw, hydrophobic nanotubes with amphiphilic polymers
(e.g., phospholipid-poly(ethylene glycol) [PL-PEG]). The hydrophobic lipid
chains of PL tend to anchor onto the nanotube surface strongly, while the
hydrophilic PEG chains afford CNT water solubility and biocompatibility.
Recently, the research group exploited this functionalisation through the
incorporation of SWCNTs with branched polymers based on poly(γ-glutamic
acid) (γPGA) and poly(maleic anhydride- alt -1-octadecene) (PMHC18)
(Fig. 9.6) . More precisely, they took advantage of the carboxylate function
of γPGA to incorporate lipophilic moieties (e.g., PL or pyrene [Py]) that can