Chemistry Reference
In-Depth Information
Etoposide
O
O
OCH
3
O
OH
OH
OCH
3
OO
O
O
CH
3
OH
Etoposide
This anticancer drug is an inhibitor of topoisomerase II and is currently used in the
therapy of lungs cancer, testicules cancer, leukemia, and glioblastoma. A first in vivo
study on a linear prodrug incorporating a cleavable unit released etoposide via some
cascade reactions [233]. The multiple events were triggered by a catalytic antibody
38C2 (a retro aldol). Another study prior to use dendrimers was achieved in the
presence of a carboxylesterase toward the hydrolysis of a prodrug containing a
carbonate function to be hydrolyzed [234].
13.3.1.6 Cancer Polytherapy with Dendrimers The concept of tritherapy against
cancer cells was reported in an elegant work of Shabat and coworkers using
camptothecin, doxorubicin, and etoposide attached to single chemical adaptor
unit [191]. Triggering the process by catalytic antibody 38C2, it was possible to
release three different drugs (CPT, DOX, and etoposide) in a cascade reaction. The
heterodendritic trimeric prodrug was more potent than individual monomeric drugs
when incubated with the antibody and tested against three cancer cell lines respon-
sible for leukemia (Scheme 13.10). This work was an extension of a similar
bioactivation method using self-immolative heterodendritic prodrugs in bitherapy
(DOX and CPT) [197b].
13.3.1.7 Multifunctional Anticancer Dendritic Platforms as Nanodevices The
most advanced and complex syntheses of dendritic nanodevices as a platform for a
selective drug delivery include several functional units bound to a commercial
dendritic scaffold (PAMAM, DAB, PEI, PPI, polyglycerol, Boltorn
) as shown in
Figure 13.9.
Each units could have a function for imaging (with a fluorescent ligand such as
FITC or a NIR ligand), for targeting cancer cells and tumors (folic acid, etc.), for
solubilizing the device (with some nontoxic, nonimmunogenic groups), for
transporting or for encapsulating a drug (PEG, alkyl chain, acetyl groups, etc.),
or for destroying cancer cells with an anticancer drug conjugate such as MTX,
DOX, CPT, and so on (Figure 13.10). For an excellent review in this field, Paleos
et al. gathered a nice compilation of such dendritic devices [106]. Tomalia et al.
also reported some guidelines for a multipurpose nanodevice for cancer therapy
and imaging [204].
