Self-Assembly of Copper-DNAzyme Nanohybrids for Dual-Catalytic Tumor Therapy

Abstract

Despite the great efforts of using DNAzyme for gene therapy, its clinical success is limited by the lack of simple delivery systems and limited anticancer efficacy. Here, we develop a simple approach for the synthesis of hybrid nanostructures that exclusively consist of DNAzyme and Cu²⁺ with ultra-high loading capacity. The Cu-DNAzyme nanohybrids allow to effectively co-deliver DNAzyme and Cu²⁺ into cancer cells for combinational catalytic therapy. The released Cu²⁺ can be reduced to Cu⁺ by glutathione and then catalyze endogenous H₂ O₂ to form cytotoxic hydroxyl radicals for chemodynamic therapy (CDT), while the 10-23 DNAzyme enables the catalytic cleavage of VEGFR2 mRNA and activates gene silencing for gene therapy. We demonstrate that the system can efficiently accumulate in the tumor and exhibit amplified cascade antitumor effects with negligible systemic toxicity. Our work paves an extremely simple way to integrate DNAzyme with CDT for the dual-catalytic tumor treatment.

Keywords: DNAzyme; Fenton-like reaction; chemodynamic therapy; gene therapy; nanohybrid.