biostudies-literatureUnknown13(26)You YAs 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 endogenChemical science7829-7836https://www.ebi.ac.uk/biostudies/studies/S-EPMC9258401biostudies-literatureA DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy.PMC9258401Liu HYou YZhu JRen JQu XWang YPu FfalseA DNAzyme-augmented bioorthogonal catalysis system for 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 endogen2022-01-01T00:00:00Z2022 Jul2025-04-05T14:24:49.777Z2025-04-05T14:24:49.777ZS-EPMC92584013586589710.1039/d2sc02050e