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Polymer Therapeutics I pp 59–94Cite as

Domino Dendrimers

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Part of the book series: Advances in Polymer Science ((POLYMER,volume 192))

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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Authors and Affiliations

  1. School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, 69978, Tel Aviv, Israel

    Roey J. Amir & Doron Shabat

Authors
  1. Roey J. Amir
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  2. Doron Shabat
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Correspondence to Doron Shabat .

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Ronit Satchi-Fainaro Ruth Duncan

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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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