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increasing the rate of hydrolysis by promoting some local polar environments of the
dendrimer [149].
13.2.3.7 Generation Number and Size Hydrolysis of dendrimers is often faster
for lower generation dendrimers. Dendrons are even degraded faster than dendrimers
because of their open structure. It is found that the degradation rate depends upon the
steric hindrance, and the bulkiness of the structural elements. To some extent, a dense
and compact higher generation dendrimer apparently protects labile functions from
hydrolysis. For instance, the synthesis of some cationic dendrimers having ammo-
nium groups at their periphery and some ester functions as labile groups were studied.
Their hydrolysis occurred at 37
CinD
2
O. The important point is that the dendrons
were all cleaved after a month, but some dendrimers remained. A faster degradation
occurred with lower generation dendrimers fromG0 to G2 [183]. Dendrons with open
structures and a higher conformational mobility were thus hydrolyzed faster than
dendrimers. A similar general trend was observed in the release of some fragrances by
Hayes and coworkers [170]. As for some innovativemeans to effect the degradation of
dendrimers, we can cite thework of Cordova and Janda in the surfacemodification and
the degradation of modified, polyester Boltorn
-type dendrons [184]. Catalytic
antibody 38C2 catalyzed a retro-aldol reaction for delivering some aldehyde func-
tions by an elimination reaction. To conclude, some parameters for the in vitro
degradation of dendrimers by a chemical or an enzymatic mean were recently defined
for a few classes of dendrimers, especially for polyester dendrimers. There is a need to
better define those parameters for various classes of dendrimers and linkers. Some
rare systematic studies already opened the way to this field. It could provide an
important and selective way to modulate the properties of dendrimers, and a better
mode of using their ability as covalent nanocarriers. Additionally, if dendrimers are
building blocks for assembling higher architectures, there would be a need to
sculpture them in a proper way at a supramolecular level and the general rules to
do it must be clear and well identified.
13.2.4 Cleavable Units for a Cascade Disassembly
More specific and complex cleavable units, also called “chemical adaptor systems”
[185] incorporating some “molecular triggers” have been designed for some specific
cascade or domino reactions in the cleavage of dendrimers. Those cleavable units have
previously been described in the literature, before their uses in dendrimer chemistry.
For instance, Monneret and coworkers published some anticancer prodrugs with
similar self-immolative spacers (cleavable units) as those below, for the slow release
of doxorubicin (DOX) and 5-fluorouracil (5-FU), albeit without a dendritic scaf-
fold [186]. Another work was related to CPT [187]. The concept of cleavable units,
even in a cascade reaction, was already reported in some studies on an antibody-
directed enzyme prodrug therapy (ADEPT) [188] and in improved chemical strategies
for a better targeting in cancer therapy [189].
An important historical event for the promotion of molecular triggers involved
three independent research groups reporting some “chemical adaptors units” designed
