Chemistry Reference
In-Depth Information
O
2
H
O
NH
2
H
N
O
H
OH
N
N
CO
2
HO
5
O
MTX
N
H
OH
H
2
N
NN
HO
NH
N
Anticancer Drug
N
N
H
N
Folic Acid (FA)
G5
HO
HO
OH
N
N
NH
2
4
N
Targeting
O
NH
Solubilizing
Group
HN
HO
HN
S
15
82
CO
2
H
Imaging
HO
O
O
FITC
4
FIGURE 13.10
Example of an assembly of the functional units on a dendritic platformwith a
G5 PAMAM core.
As for the targeting units, folic acid was often reported. It interacts with over-
expressed folate receptors on cancer cells. Neurotensin (a peptide) was also used in a
similar platform for fighting colon, pancreatic, prostate, and lung carcinomas [235]. A
cyclic peptide (cRGD) also made its way as a new targeting unit from the work of
Baker, Jr. and coworkers [236].
The nanodevice model containing folic acid and MTX linked to a PAMAM
scaffold is probably one of the most studied covalent combination in such a dendritic
platform from Baker et al. Another one made uses of a partially acetylated G5
PAMAM template, combined to an imaging agent (fluorescein isothiocyanate), folic
acid, and paclitaxel (taxol, an anticancer drug) [196a]. Ester linkages were used for the
delivery of taxol. A similar platform used a combination of the same units as above,
excepted MTX as an anticancer drug and a partial acetylation of G5 PAMAM [176].
The ester linkage of MTX could be achieved via a glycidol linker. The latter also
helped to eliminate the peripheral NH
2
groups for avoiding unwanted nonspecific
targetings. An amide link was also used to directly conjugate MTX to PAMAM.
A recent nanodevice model of diagnostic and imaging was based on a biodegrad-
able drug carrier from the coupling of PAMAMor PEI dendritic cores with some arms
of poly(
L
-glutamic acid), folic acid residues for targeting cancer cells, and a near-
infrared indocyanine dye [196c]. The resulting conjugate polymers could be degraded
by the endosomal enzyme cathepsin B and could selectively bind to tumor cells
expressing folate receptors. Radioiodination and fluorescence confocal microscopy
were also demonstrated for imaging cancer cells and the location and transport of a
dendritic platform incorporating doxorubicin (cell mapping of the platform) [148].
13.3.1.8
In Vivo
Studies of Some Anticancer Dendritic Platforms as Nanodevices
DOX-Boltorn
Systems Among the first advanced in vivo studies on the biological
evaluation of dendrimer were some reports on the design and the synthesis of
Boltorn
-type polyester dendrimers for DOX delivery (Figure 13.11) [152].
