DNAzyme-based　gene　regulation　shows　great　potential　for　the　therapy　of　many　cancers.　However,　inef-fective　delivery　and　insufficient　cofactor　supply　pose　challenges　for　potent　gene　therapy.　In　this　study,　we　constructed　a　smart　metal-polyphenol-DNAzyme　nanoplatform　(TA-Mn@Dz　NPs)　with　intrinsic　stabil-ity,　effective　delivery,　and　cofactor　self-supply　ability　for　gene-chemodynamic　synergistic　tumor　therapy.　Tannic　acid,　a　plant-derived　polyphenol,　acts　as　an　intermediate　structural　unit　to　mediate　the　assem-bly　of　Mn2+/DNAzyme　and　tumor　acid　environment-responsive　nanocarriers.　Intracellularly,　the　acidic　environment　triggers　the　decomposition　of　TA-Mn@Dz　NPs　to　release　DNAzyme　and　Mn2+.　The　Mn2+　ion　not　only　boosts　the　catalytic　cleavage　of　surviving　mRNA　for　effective　gene　therapy　but　also　acti-vates　chemodynamic　therapy　(CDT),　generating　highly　toxic　&　BULL;OH　from　endogenous　H2O2.　When　tail　in-travenously　injected　into　MCF-7　tumor-bearing　mice,　the　TA-Mn@Dz　NPs　display　desirable　synergistic　gene-chemodynamic　antitumor　effects,　paving　the　way　for　developing　DNAzyme-based　multifunctional　theranostic　platforms　for　biomedical　applications.Statement　of　significance1.　A　smart　metal-polyphenol-DNAzyme　nanoplatform　was　constructed　for　gene-chemodynamic　syner-gistic　tumor　therapy.　2.　Tannic　acid　act　as　intermediate　structural　units　to　mediate　the　assembly　of　Mn2+/DNAzyme　and　tumor　acid　environment-responsive　nanocarriers.　3.　The　Mn2+-ion　could　not　only　boost　the　catalytic　cleavage　of　surviving　mRNA　for　effective　gene　therapy,　but　also　catalyze　endogenous　H2O2　to　form　cytotoxic　hydroxyl　radicals　for　chemodynamic　therapy.　4.　Our　work　paves　an　extremely　simple　way　to　integrate　gene　therapy　with　CDT　for　the　dual-catalytic　tumor　treatment.&　COPY;　2023　Acta　Materialia　Inc.　Published　by　Elsevier　Ltd.　All　rights　reserved.