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Self‐Assembly of Copper–DNAzyme Nanohybrids for Dual‐Catalytic Tumor Therapy
Author(s) -
Liu Congzhi,
Chen Yaoxuan,
Zhao Jian,
Wang Yong,
Shao Yulei,
Gu Zhanjun,
Li Lele,
Zhao Yuliang
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202101744
Subject(s) - deoxyribozyme , chemistry , catalysis , genetic enhancement , nanotechnology , cancer therapy , biophysics , combinatorial chemistry , cancer research , gene , biochemistry , materials science , cancer , dna , biology , genetics
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 Cu 2+ with ultra‐high loading capacity. The Cu–DNAzyme nanohybrids allow to effectively co‐deliver DNAzyme and Cu 2+ into cancer cells for combinational catalytic therapy. The released Cu 2+ can be reduced to Cu + by glutathione and then catalyze endogenous H 2 O 2 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.