Issue 26, 2022

Host–guest interaction-based supramolecular prodrug self-assemblies for GSH-consumption augmented chemotherapy

Abstract

The over-expressed cellular glutathione (GSH) severely restricts the chemotherapeutic efficacy due to the GSH-induced detoxification of chemical drugs. Herein, how to construct effective drug delivery systems with GSH-consumption property is still a general concern and a major challenge. In this study, the host–guest interactions between water-soluble pillar[6]arene (WP[6]) and chlorambucil-arylboronic acid (Cb-BA) were utilized to construct supramolecular prodrug self-assemblies (SPSAs) with specific stimuli-responsive property. Notably, the BA moiety could not only consume GSH but also rapidly bind curcumin (Cur), which could inhibit the thioredoxin reductase (TrxR) to further reduce the GSH biosynthesis pathway. Benefiting from the functionality of BA-Cur conjugates, the GSH levels could be significantly downregulated, paving a novel way to enhance chemotherapeutic efficacy. In vitro and in vivo investigations demonstrated that this two-pronged GSH-depletion strategy could amplify the cellular oxidative stress and achieve excellent anti-tumor efficacy.

Graphical abstract: Host–guest interaction-based supramolecular prodrug self-assemblies for GSH-consumption augmented chemotherapy

Supplementary files

Article information

Article type
Paper
Submitted
06 Cax 2022
Accepted
03 Qas 2022
First published
06 Qas 2022

J. Mater. Chem. B, 2022,10, 4952-4958

Host–guest interaction-based supramolecular prodrug self-assemblies for GSH-consumption augmented chemotherapy

Y. Bai, X. Li, M. Li, Q. Shang, J. Yang, L. Fan and W. Tian, J. Mater. Chem. B, 2022, 10, 4952 DOI: 10.1039/D2TB00989G

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