Direct Real-Time Monitoring of Prodrug Activation by Chemiluminescence

Samer Gnaim, Anna Scomparin, Sayantan Das, Rachel Blau, Ronit Satchi-Fainaro, Doron Shabat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal-to-noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β-galactosidase. The activation of the prodrug in the presence of β-galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β-galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β-galactosidase-overexpressing tumor-bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment.

Original languageEnglish
Pages (from-to)9033-9037
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number29
DOIs
StatePublished - 16 Jul 2018

Funding

FundersFunder number
German Israeli Foundation
Israeli Ministry of Science and Technology
United States-Israel Binational Science Foundation
Israel Science Foundation
Council for Higher Education

    Keywords

    • chemiluminescence
    • fluorescence probes
    • molecular imaging
    • prodrugs
    • theranostics

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