A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

Yawen You; Hao Liu; Jiawei Zhu; Yibo Wang; Fang Pu; Jinsong Ren; Xiaogang Qu

doi:10.1039/d2sc02050e

A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

Chem Sci. 2022 Jun 10;13(26):7829-7836. doi: 10.1039/d2sc02050e. eCollection 2022 Jul 6.

Authors

Yawen You^{1

2}, Hao Liu^{1

2}, Jiawei Zhu^{1

2}, Yibo Wang³, Fang Pu^{1

2}, Jinsong Ren^{1

2}, Xiaogang Qu^{1

2}

Affiliations

¹ State Key Laboratory of Rare Earth Resources Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun 130022 P. R. China pufang@ciac.ac.cn jren@ciac.ac.cn xqu@ciac.ac.cn.
² University of Science and Technology of China Hefei Anhui 230029 P. R. China.
³ Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun 130022 P. R. China.

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.