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Conventional nanomedicines lack the autonomous capability to navigate these evolving obstacles. Here, we engineer a DNA\u2011based nanorobot constructed on an optimized tetrahedral framework nucleic acid (tFNA) that co\u2011assembles tumor\u2011targeting aptamers, catalytic platinum nanoparticles (Pt\u2011NPs), and the therapeutic payload methylene blue (MB) into a single modular platform. This integrated design enables three coordinated functions: tumor\u2011specific recognition, self\u2011propelled transport driven by oxygen generation, and concurrent hypoxia alleviation to potentiate photodynamic therapy (PDT) in hypoxic tumors. The Pt\u2010NPs catalyze the decomposition of overproduced hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) in the tumor microenvironment, generating oxygen bubbles that both drive deep tissue penetration (to depths\u00a0&gt;\u00a0300\u00a0\u00b5m) and alleviate local hypoxia. This self\u2011powered propulsion enables efficient delivery of MB, leading to cascaded PDT activation. In vivo, the nanorobot achieves 85% tumor regression through the coordinated actions of deep penetration, hypoxia relief, and enhanced PDT. This modular DNA nanoplatform provides a promising strategy for advanced nanomedicine by autonomously addressing key delivery barriers in solid tumor therapy.\n                  <\/jats:p>","DOI":"10.1002\/anie.7173496","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:31:41Z","timestamp":1790425901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Self\u2010Propelled DNA\u2010Based Nanorobot for Hypoxic Tumor Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-0889","authenticated-orcid":false,"given":"Qin","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory for Flexible Electronics (LoFE) Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology Institute of Advanced Materials (IAM) Nanjing University of Posts and Telecommunications  Nanjing 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Institute of Advanced Materials (IAM) Nanjing University of Posts and Telecommunications  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Flexible Electronics (LoFE) Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology Institute of Advanced Materials (IAM) Nanjing University of Posts and Telecommunications  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7171-7338","authenticated-orcid":false,"given":"Chunhai","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering New Cornerstone Science Laboratory Frontiers Science Center for Transformative Molecules National Center for Translational Medicine Zhangjiang Institute for Advanced Study Shanghai Jiao Tong University  Shanghai 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