Biomedical Engineering Reference
In-Depth Information
In general, the covalent functionlisation of nanotubes is more robust
and better controllable compared with procedures based on non-covalent
methods, and it offers the possibility of introducing multiple functionalities.
In particular, some strategies to integrate multiple groups on the tubes'
sidewalls have been developed. One of them consists in the application of
1,3-dipolar cycloaddition to introduce
N
-functionalised pyrrolidine rings on
the external walls of the tubes. Two orthogonally protected
α
-amino acids
were introduced in the presence of paraformaldehyde. Selective elimination of
the phthalimidic group (Pht) in ethanolic hydrazine allowed the introduction
of the luorescent molecule (FITC), while the acidic conditions removed
the
tert
-butyloxycarbonyl (Boc) group and permitted the coupling of the
generated free amino function with the activated
α
or
γ
carboxylic group of
the anticancer drug methotrexate (MTX) (Scheme 2.5).
86
O
O
H
O
O
N
Boc-NHCH
2
COOH/(CH
2
O)n
DMF,130 °C
O
N
O
N
O
O
Hydrazine in EtOH
FITC in DMF
N
N
N
NH
2
A,G
O
N
N
O
O
O
Glu-NH
NH
2
O
O
H
O
H
N
N
O
OH
OH
HCl 4M in dioxane
MTX, Bop/DIEA
in DMF.
O
O
H
N
H
N
N
N
N
N
O
O
O
HO
2
C
O
HO
2
C
S
S
O
O
Scheme 2.5
MTX-FITC-functionalized carbon nanotubes.
Reagents: (a) R-
NHCH
2
COOH/(CH
2
O)
n
in DMF, 130 °C; (b) hydrazine in EtOH; (c) FITC in DMF; (d) HCl
4 M in dioxane; (e) MTX, Bop/DIEA in DMF.
MTX is a drug that is widely used against cancer, but it displays toxic
side effects and a reduced cellular uptake.
123
The limited capacity of MTX to
cross the cell membrane was overcome by conjugating it to
f
-CNTs, which are
capable to enhance cell uptake of linked moieties. The presence of luorescent
tubes inside the cells around the nuclear membrane and the time and dose
dependence of the internalization process have been demonstrated.
In a slightly different approach, MWCNTs have been functionalised
with
amphotericin B (AmB), which is a potent antimycotic drug normally used for
the treatment of chronic fungal infections.
87
However, AmB displays also a
remarkable toxicity towards mammalian cells,
124
presumably because of its
low water solubility and its tendency to form aggregates
125
(Scheme 2.6).
Search WWH ::
Custom Search