Thioguanine-Coordinated Assembly for Synthetic Lethality of Colorectal Cancer with Defective Mismatch Repair

Abstract

A thioguanine-coordinated metal-organic polymer was designed for the carrier-free co-delivery of thioguanine and Werner syndrome helicase (WRN) inhibitor to induce synthetic lethality in colorectal cancer cells with defective mismatch repair. Upon glutathione-triggered disassembly of the nanovector, the released thioguanine and WRN inhibitor concurrently disrupted both primary and compensatory DNA damage response pathways, achieving significant synthetic lethality.

Supplementary files

Article information

Article type
Communication
Submitted
27 Mar 2025
Accepted
01 Jul 2025
First published
02 Jul 2025

Chem. Commun., 2025, Accepted Manuscript

Thioguanine-Coordinated Assembly for Synthetic Lethality of Colorectal Cancer with Defective Mismatch Repair

X. Xu, Z. Yang, Z. Xu, T. Wu, L. Wu and J. Lei, Chem. Commun., 2025, Accepted Manuscript , DOI: 10.1039/D5CC01724F

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