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Evaluation of a GSH-targeting prodrug via a sulfonamide-induced “integrative” platform for selective cancer therapy

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Abstract

A sulfonamide-appended gemcitabine prodrug was newly produced. The prodrug was shown to efficiently distinguish GSH from cysteine and homocysteine. Upon reaction of this prodrug with GSH, which is relatively abundant in tumor cells, sulfonyl group cleavage occurred as well as active release of the drug GMC and a concomitant increase in the innate fluorescence intensity. As a proof of concept, colocalization experiments were carried out; these experiments demonstrated that the probe LHX resulted in, via receptor-mediated endocytosis, significantly improved therapeutic efficacy and few side effects. Thus, these results indicated the theranostic agent to be a promising “integrative” platform for efficient cancer therapy. The agent can be activated in real time, and not only be selectively monitored and localized by specific tumour cells, but also undergo cascaded cleavage to induce both a fluorogenic response and release of an active cytotoxic drug.

Graphical abstract: Evaluation of a GSH-targeting prodrug via a sulfonamide-induced “integrative” platform for selective cancer therapy

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Supplementary files

Article information


Submitted
31 Mar 2020
Accepted
18 May 2020
First published
19 May 2020

Analyst, 2020, Advance Article
Article type
Paper

Evaluation of a GSH-targeting prodrug via a sulfonamide-induced “integrative” platform for selective cancer therapy

J. Liu and C. Cao, Analyst, 2020, Advance Article , DOI: 10.1039/D0AN00627K

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