Chemistry Reference
In-Depth Information
(b) An increase of branching diminishes the renal filtration and increases the
persistence of the dendritic prodrug.
(c) Rigid, globular macromolecules decrease the renal filtration and increase the
persistence of the prodrug in the blood stream compared to flexible and
elongated (chain) polymers.
(d) More rigid, tubular macromolecules could have a better pore penetration and a
higher accumulation in tumors.
As for an active targeting, several strategies have been put forward from the con-
jugation of some monoclonal antibodies or from some specific dendritic surface
functionalization with some targeting units, favoring cancer cell adhesion, recogni-
tion of the prodrugs and cell internalization. Among some common targeting units are
folic acid, biotin [221], neurotensin, and a cyclic peptide (cRGD) and some glyco-
sides [208]. These units (also called epitopes) are based on a specific recognition of
some receptors often overexpressed in some cancer cell lines (for instance, folic acid
is overexpressed in brain, human breast, and lung cancers).
13.3.1.5 Anticancer Dendrimer-Drug Conjugates An excellent review summa-
rized a collection of covalently bound anticancer drugs to a dendritic scaffold [222].
Some general reviews related to dendrimers in drug delivery are available, including
an important section on anticancer dendrimer conjugates [36,40,44,97,223-228].
Until now, many common anticancer drugs conjugated to dendrimers were
reported in the literature: doxorubicin (DOX), methotrexate (MTX), camptothecin
(CPT), etoposide, 5-fluorouracil (5-FU), and paclitaxel (taxol). The following sec-
tions will delineate a few representative examples of some anticancer dendritic
prodrugs using the covalent disassembly modes presented in Section 13.2.1. The
examples will also include some cleavable units for a cascade disassembly (molecular
triggers) by using a specific stimuli (for instance, a pH variation). A highlight
article [229] on self-immolative dendrimers [61] as some anticancer drug delivery
platforms based on an enzymatic triggering was reported by Shabat. Some cascade
cleavages were presented for effecting the delivery of a single, double, or triple type of
drugs for a possible bi- or tritherapy.
Doxorubicin
O
O
OH
OH
OH
CH
3
O
O
OH
O
O
NH
2
HO
Doxorubicin
