{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:49:50Z","timestamp":1791877790200,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC22274044"],"award-info":[{"award-number":["NSFC22274044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22534001"],"award-info":[{"award-number":["22534001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small Methods"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Therapy\u2010induced senescence (TIS) promotes tumor resistance and recurrence through the senescence\u2010associated secretory phenotype (SASP), but achieving tumor cell\u2010selective senescence modulation remains a formidable challenge due to limited cellular specificity, insufficient spatiotemporal control, and the complexity of the secretory program. Here, we develop a self\u2010reporting hierarchical DNA nanoplatform (Gal\u2010lipo@S\u2010CHA) that enables selective senescence reprogramming and immune remodeling in TIS tumor cells. In this design, a newly engineered \u03b2\u2010galactosidase\u2010responsive charge\u2010reversal lipid carrier establishes the first layer of senescence selectivity by enabling preferential delivery and enhanced endosomal escape of a hierarchically gated catalytic DNA circuit. Subsequent intracellular decoding of GSH and microRNA\u201021, two tumor\u2010associated and senescence\u2010enriched molecular signatures, provides a second layer of tumor cell selectivity, activating the circuit specifically in pathological senescent tumor cells. The activated circuit simultaneously generates a fluorescence signal for real\u2010time monitoring and assembles an NF\u2010\u03baB decoy to block NF\u2010\u03baB nuclear translocation, thereby suppressing downstream pro\u2010tumorigenic SASP production at the upstream regulatory source. In vivo studies demonstrate that Gal\u2010lipo@S\u2010CHA effectively remodels the tumor immune microenvironment by enhancing natural killer cell infiltration and M1 macrophage polarization. Collectively, this framework establishes a new paradigm for selectively reprogramming pathological senescence, providing a versatile platform to support immunomodulatory cancer therapies.<\/jats:p>","DOI":"10.1002\/smtd.71110","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:33:23Z","timestamp":1791876803000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Self\u2010Reporting Hierarchical DNA Nanoplatform for Tumor Cell\u2010Selective Senescence Modulation and Immune Remodeling"],"prefix":"10.1002","author":[{"given":"Wenya","family":"Dang","sequence":"first","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Da","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolan","family":"Hu","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Xie","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wu","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jili","family":"Li","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1757-6810","authenticated-orcid":false,"given":"Yanlan","family":"Liu","sequence":"additional","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"39","article-title":"The Great Escape: Tumour Cell Plasticity in Resistance to Targeted Therapy","volume":"19","author":"Boumahdi S.","year":"2020","journal-title":"Nature Reviews: Drug Discovery"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007690\u20109"},{"key":"e_1_2_9_4_1","first-page":"323","article-title":"Therapy Resistance: Opportunities Created by Adaptive Responses to Targeted Therapies in Cancer","volume":"22","author":"Labrie M.","year":"2022","journal-title":"Nature Reviews: Cancer"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.05.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010020\u20100286\u2010z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010025\u201002419\u20102"},{"key":"e_1_2_9_8_1","first-page":"340","article-title":"Exploiting Senescence for the Treatment of Cancer","volume":"22","author":"Wang L.","year":"2022","journal-title":"Nature Reviews: Cancer"},{"key":"e_1_2_9_9_1","first-page":"51","article-title":"Senescence in Tumours: Evidence From Mice and Humans","volume":"10","author":"Collado M.","year":"2010","journal-title":"Nature Reviews: 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