Abstract
Domino dendrimers have recently been developed and introduced as a potential platform for a single triggered multi-prodrug. Surprisingly, three independent groups reported similar concepts almost simultaneously. These unique structural dendrimers can release all of their tail units, through a domino-like chain fragmentation, which is initiated by a single cleavage at the dendrimer's core. This chapter reviews the recent efforts to design domino-like dendrimers with emphasis on the application of drug delivery. Incorporation of drug molecules as the tail units and an enzyme substrate as the trigger, can generate a multi-prodrug unit that is activated with a single enzymatic cleavage. Dendritic prodrugs, activated through a single catalytic reaction by a specific enzyme, could present significant advantages in the inhibition of tumor growth, especially if the targeted or secreted enzyme exists at relatively low levels in the malignant tissue. Domino dendrimers may also be applied as a general platform for biosensor molecules, used to detect enzymatic activity.
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Abbreviations
- AB2:
-
three arm star dendritic subunit
- AB3:
-
four arm star dendritic subunit
- ALL:
-
acute lymphoblastic leukemia
- AML:
-
acute myeloid leukemia
- Boc:
-
t-butoxycarbonyl
- CPT:
-
campthotecin
- DOX:
-
doxorubicin
- HEL:
-
human erythroleukemia cell line
- HL-60:
-
human acute myeloid leukemia cell line
- IC50 :
-
inhibition concentration (at 50%)
- MOLT-3:
-
human T-lineage acute lymphoblastic leukemia cell line
- PBS:
-
phosphate buffered saline
- PGA:
-
penicillin G amidase
- mCPT:
-
monomeric CPT dendritic prodrug
- tCPT:
-
trimeric CPT dendritic prodrug
- TFA:
-
trifluoroacetic acid
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Amir, R.J., Shabat, D. Domino Dendrimers. In: Satchi-Fainaro, R., Duncan, R. (eds) Polymer Therapeutics I. Advances in Polymer Science, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_021
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DOI: https://doi.org/10.1007/12_021
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