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Equipping adoptive cells with multifunctional modules for function enhancement and real-time efficacy readouts is a key solution but remains challenging due to the dynamic nature of the cell membrane and the limited accessibility of available binding sites on the membrane. Herein, we report a multimodule intelligent NK (MI-NK) cell that encapsulates NK cells within a durable DNA scaffold anchored with multiple adaptable functional modules, including a barrier penetration module (glucose oxidase-catalase cascade enzymes), an activity boosting module (IL-21 nanoparticles), and an efficiency reporting module (granzyme B-activatable hemicyanine NIR fluorescent probe). Oxygen generated from cascade enzymatic reactions drives MI-NK cells and promotes their tumor infiltration. IL-21 nanoparticles are disintegrated by GSH to release IL-21 for on-site NK cell activation and expansion. Activated NK cells secrete granzyme B, which restores the NIR fluorescence of the efficiency-reporting module to enable response reporting as early as 6 h after adoptive cell administration. The as-obtained MI-NK effectively enhances the in vivo immunotherapeutic efficiency. The types and proportions of adaptable modules can be expanded, offering a universal approach for adoptive cell therapy efficiency.<\/jats:p>","DOI":"10.1021\/acsnano.6c10559","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:04:36Z","timestamp":1788462276000},"page":"25572-25593","source":"Crossref","is-referenced-by-count":0,"title":["A\nDNA-Scaffolded\nNatural Killer Cell with Adaptable\nMultimodules for Enhanced Immunotherapy and Early Efficiency Reporting"],"prefix":"10.1021","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4381-4514","authenticated-orcid":true,"given":"Chengfeng","family":"Cai","sequence":"first","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicong","family":"Chao","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-5302","authenticated-orcid":true,"given":"Huangxian","family":"Ju","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5718-7804","authenticated-orcid":true,"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"issue":"1","key":"2026092210083052300_cit1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12943-023-01797-9","article-title":"Nanomaterials\nin tumor immunotherapy: new strategies and challenges","volume":"22","author":"Zhu","year":"2023","journal-title":"Mol. 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Immunol."},{"issue":"4","key":"2026092210083052300_cit5","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41423-024-01145-x","article-title":"Development of NK cell-based\ncancer immunotherapies through receptor engineering","volume":"21","author":"Page","year":"2024","journal-title":"Cell. Mol. Immunol."},{"issue":"1","key":"2026092210083052300_cit6","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13045-022-01375-4","article-title":"Drugging\nKRAS:\ncurrent perspectives and state-of-art review","volume":"15","author":"Parikh","year":"2022","journal-title":"J. Hematol. 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