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Constructing multivalent ligands with sufficient fluid stability in complex environments remains a challenge. Herein, we develop a tetrahedral DNA framework (TDF) ensembled multivalent aptamers (TEA\n                    <jats:sub>n<\/jats:sub>\n                    , n = 1\u20133) with programmable ligands size, enabling efficient capture of circulating tumor cells (CTCs) and accurate monitoring of clinical treatment progress. The precisely structured TEA\n                    <jats:sub>n<\/jats:sub>\n                    ensures the size\u2010matching and cooperative hybridization with epithelial cell adhesion molecule (EpCAM) on cell membrane. Compared to traditional aptamer approach, the dissociation constants (K\n                    <jats:sub>d<\/jats:sub>\n                    ) of TEA\n                    <jats:sub>3<\/jats:sub>\n                    exhibits \u223c20\u2010fold growth in serum due to its precise size and rigid DNA framework. This high\u2010affinity interaction significantly enhances capture efficiency by improving fluid stability of TEA\n                    <jats:sub>n<\/jats:sub>\n                    and magnetic beads complex in complex environment. In addition, this CTC detection strategy is applied for clinical tumor treatment evaluation and progress monitoring in liver cancer patient samples, achieving an accuracy of \u223c83.3% in classifying patients as complete or partial responses (CR\/PR). Overall, this strategy will strongly promote potential clinical application of DNA framework for cancer diagnosis and disease progression monitoring.\n                  <\/jats:p>","DOI":"10.1002\/anie.202425252","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:06:39Z","timestamp":1741741599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["DNA Framework\u2010Ensembled Aptamers Enhance Fluid Stability in Circulating Tumor Cells Capture for Tumor Treatment Evaluation"],"prefix":"10.1002","volume":"64","author":[{"given":"Yirong","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Interventional Oncology Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenzhou","family":"Mao","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Interventional Oncology Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhai","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"},{"name":"School of Chemistry and Chemical Engineering New Cornerstone Science Laboratory Frontiers Science Center for Transformative Molecules Zhangjiang Institute for Advanced Study and National Center for Translational Medicine Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zuo","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"},{"name":"School of Chemistry and Chemical Engineering New Cornerstone Science Laboratory Frontiers Science Center for Transformative Molecules Zhangjiang Institute for Advanced Study and National Center for Translational Medicine Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0996-1116"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2022.101516"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","unstructured":"L.Wang P.Quan S. 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