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In the current contribution, we propose a structural DNA nanotechnology (TMM) for the construction of a degradation\u2010resistant DNA nanotube (DNT) via periodically tiling two structural modules (M) into a modularized (M) tubular DNA nano\u2010architecture. The tube circumference is 118.6\u00a0nm, the tube length is 478\u00a0nm and the assembly efficiency is almost up to 90%. Upon installation of up\u2010down tumor cell\u2010binding aptamers onto each structural module in a highly precise manner, a protective outer layer was formed. Compared with Biotin\u2010DNA nanowire, the relative nuclease degradation resistance of AS1411\u2010DNT is improved by about 92\u2010fold. Via using commercially synthesized 5\u2010FU\u2010embedded DNA components, we constructed a tumor cell\u2010targeting therapeutic agent\u2010loaded nanoconjugate, AS1411\u2010DNT\u20105\u2010FU, which exhibits significantly higher therapeutic outcomes than clinic free 5\u2010FU in MCF\u20107 tumor\u2010bearing mouse models without observable systemic toxicity. While DNA DNT holds great potential for precise drug delivery for cancer therapy, the modularization\u2010based TMM structural DNA nanotechnology is expected to promote the development of next\u2010generation multifunctional 3D\u2010DNA nanostructures and clinical application in precision medicine.<\/jats:p>","DOI":"10.1002\/smll.75108","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:35:44Z","timestamp":1786959344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potentiating In Vivo Precision Cancer Therapy With Modularized Aptamer\u2010Chemotherapeutics Conjugates Based on DNA Tiling\u2010Mediated Structural Nanotechnology"],"prefix":"10.1002","volume":"22","author":[{"given":"Weijun","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"},{"name":"College of Chemistry and Food Science Nanchang Normal University  Nanchang China"},{"name":"Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Wu","sequence":"additional","affiliation":[{"name":"Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6202-8006","authenticated-orcid":false,"given":"Wenhao","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-282X","authenticated-orcid":false,"given":"Zai\u2010Sheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2991\/jegh.k.191008.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2016.17.S3.43"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21863"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.06.023"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008276\u20101"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20240037"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202214655"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.09.166"},{"issue":"16","key":"e_1_2_8_11_1","first-page":"e18035","article-title":"Nanoemulsions Loaded With 5\u2010fluorouracil and Curcumin as a Strategy for Enhancing Anticancer Activity in FaDu Cells for Treating Oral Cancer","volume":"43","author":"Sahoo P. 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