Issue 26, 2022

A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

Abstract

As one of the representative bioorthogonal reactions, the copper-catalyzed click reaction provides a promising approach for in situ prodrug activation in cancer treatment. To solve the issue of inherent toxicity of Cu(I), biocompatible heterogeneous copper nanoparticles (CuNPs) were developed for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. However, the unsatisfactory catalytic activity and off-target effect still hindered their application in biological systems. Herein, we constructed a DNAzyme-augmented and targeted bioorthogonal catalyst for synergistic cancer therapy. The system could present specificity to cancer cells and promote the generation of Cu(I) via DNAzyme-induced value state conversion of DNA-templated ultrasmall CuNPs upon exposure to endogenous H2O2, thereby leading to high catalytic activity for in situ drug synthesis. Meanwhile, DNAzyme could produce radical species to damage cancer cells. The synergy of in situ drug synthesis and chemodynamic therapy exhibited excellent anti-cancer effects and minimal side effects. The study offers a simple and novel avenue to develop highly efficient and safe bioorthogonal catalysts for biological applications.

Graphical abstract: A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

Supplementary files

Article information

Article type
Edge Article
Submitted
11 apr 2022
Accepted
09 iyn 2022
First published
10 iyn 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 7829-7836

A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

Y. You, H. Liu, J. Zhu, Y. Wang, F. Pu, J. Ren and X. Qu, Chem. Sci., 2022, 13, 7829 DOI: 10.1039/D2SC02050E

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