4.8 Article

A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

Journal

CHEMICAL SCIENCE
Volume 13, Issue 26, Pages 7829-7836

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d2sc02050e

Keywords

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Funding

  1. National Key R&D Program of China [2021YFF1200701, 2019YFA0709202]
  2. National Nature Science Foundation of China [21871249, 21820102009, 91856205, 21977091, CAS QYZDJ-SSW-SLH052]
  3. Jilin Province Science and Technology Development Plan Project [20200201241JC]

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This study developed a DNAzyme-augmented and targeted bioorthogonal catalyst that exhibits specificity to cancer cells and promotes the generation of Cu(i) for in situ drug synthesis. The DNAzyme also damages cancer cells, resulting in synergistic cancer therapy.
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.

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