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Herein we report a DNA nanocomplex containing cascade DNAzymes and promoter\u2010like Zn\u2010Mn\u2010Ferrite (ZMF), achieving combined gene\/chemo\u2010dynamic therapy. The promoter\u2010like ZMF decomposed in response to intratumoral glutathione to release a sufficient quantity of metal ions, thus promoting cascade DNA\/RNA cleavage and free radical generation. Two kinds of DNAzymes were designed for sequential cascade enzymatic reaction, in which metal ions functioned as cofactors. The primary DNAzyme self\u2010cleaved the DNA chain with Zn\n                    <jats:sup>2+<\/jats:sup>\n                    as cofactor, and produced the secondary DNAzyme; the secondary DNAzyme afterwards cleaved the EGR\u20101 mRNA, and thus downregulated the expression of target EGR\u20101 protein, achieving DNAzyme\u2010based gene therapy. Meanwhile, the released Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , Mn\n                    <jats:sup>2+<\/jats:sup>\n                    and Fe\n                    <jats:sup>2+<\/jats:sup>\n                    induced Fenton\/Fenton\u2010like reactions, during which free radicals were catalytically generated and efficient chemo\u2010dynamic therapy was achieved. In a breast cancer mouse model, the administration of DNA nanocomplex led to a significant therapeutic efficacy of tumor growth suppression.\n                  <\/jats:p>","DOI":"10.1002\/anie.202113619","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T22:00:51Z","timestamp":1638741651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["A DNA Nanocomplex Containing Cascade DNAzymes and Promoter\u2010Like Zn\u2010Mn\u2010Ferrite for Combined Gene\/Chemo\u2010dynamic Therapy"],"prefix":"10.1002","volume":"61","author":[{"given":"Chi","family":"Yao","sequence":"first","affiliation":[{"name":"Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) Institute of Biomolecular and Biomedical Engineering School of Chemical Engineering and Technology Tianjin University  Tianjin 300350 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Australian Centre for, NanoMedicine University of New South Wales  Sydney NSW 2052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2634-9281","authenticated-orcid":false,"given":"Dayong","family":"Yang","sequence":"additional","affiliation":[{"name":"Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) Institute of Biomolecular and Biomedical Engineering School of Chemical Engineering and Technology Tianjin University  Tianjin 300350 P. R. 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