Chemistry Reference
In-Depth Information
A pH responsive polyglycerol dendrimer was acetylated and used as a supramo-
lecular carrier of a Congo red dye. The latter inclusion complex was stable at basic or
neutral pH for months but the molecular cargo was released at pH
3 when the
acetylated shell was cleaved [90]. Ketals have been less often reported in the field of
cleavable dendrimers. They were interesting intermediates and protective groups in
the synthesis of “bow-tie dendrimers” [150].
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Imino Functions (pH Responsive Dendrimers) Hydrazones were also useful as a
pH-sensitive linker for the release of methotrexate as an anticancer drug or folic acid
from some poly(aryl ether) dendrimers [151]. Another work using Boltorn
-type
polyester dendrimers also indicated that doxorubicin could be released using hy-
drazone linkers [115,152].
Imines are usually easily cleaved under acidic and almost neutral pH (especially
alkylated imines). Haag and coworkers used water-soluble pH responsive dendritic
core-shell nanocarriers of polar dyes based on the covalent attachment of PEG chains
to a PEI core dendrimer via some imino functions. This model helped to release the
encapsulated guest by cleaving the PEG chains [89]. In a similar manner, they used
imines with long alkyl chains with a Congo red dye as a guest. The sensitivity to pH
was higher than for acetals [90].
Disulfides (Redox Responsive Dendrimers) The disulfide linker has been reviewed
in the field of drug delivery, albeit without the involvement of dendrimers [153]. It has
already found several uses in medicinal chemistry and related biological fields.
Very recently, disulfides appeared as a useful linker in dendrimer chemistry that can
be cleaved under mild reductive conditions with thiols (glutathione, cysteine,
dithiothreitol, etc.). Most examples involved PAMAM-cystamine dendrimers. For
instance, some low molecular weight dendrons were used to bind DNA and release
their cargo by an in vitro reductionwith dithiothreitol (DTT), as amimic to glutathione
(GSH) found in the cytoplasm of a cell [154]. In this way, it could provide a new
generation of vectors for gene delivery with DNA. A PAMAM dendrimer conjugated
to N-acetylcysteine (NAC) via a disulfide linkage was reported [155]. NAC is a
neuroantiinflammatory and antioxidant therapeutic. The release of NAC after reacting
with cysteine and GSH was successfully investigated at various pH. The release was
faster at physiological pH 7.4 compared to lysosomal pH 5. However, bovine serum
albumin containing a cysteine residue did not cleave the conjugate. In a similar study,
N-acetyl-
L
-cysteine (NAC) was conjugated to PAMAM dendrimers as cationic G4-
NH
4
or anionic G3.5-CO
2
H PAMAM dendrimers and tested against intracellular
GSH. NAC was released within 1 h at GSH 10mM. The antioxidant properties were
also followed as an indirect measure of NAC release in microglial cells. A PAMAM
dendrimer was decorated with PEG and cysteines that could form disulfides at their
periphery [156]. Inclusion complexes were tried with rose bengal.
Cystamine core PAMAMdendrimers are commercially available. Their cleavage
of the disulfide function produces two thiolated dendrons. Curcumin, a spice in
South Asian cooking, was found to have anticancer, antiinflammatory, and anti-
oxidant properties. It was conjugated to a cystamine core PAMAMdendrimer [157].
