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Oxidative stress\u2010mediated injury plays a pivotal role in driving fibrotic progression, with hepatic macrophages serving as a dominant source of reactive oxygen species (ROS). Consequently, targeted suppression of macrophage\u2010derived ROS presents a promising therapeutic strategy. Single\u2010cell RNA sequencing analysis identified Galectin\u20103 as positively correlated with macrophage oxidative stress and ROS production. Here, a dynamic DNA nano\u2010antioxidant (DDN) is developed for hepatic macrophage\u2010specific small interfering RNA (siRNA) delivery targeting Galectin\u20103. DDN administration achieved a 3.92\u2010fold reduction in Galectin\u20103 expression, with transcriptomic profiling revealing restoration of Nuclear Factor Erythroid 2\u2010Related Factor 2 (NRF2) signaling and consequent attenuation of oxidative stress in macrophages. Pharmacokinetic assessment via IVIS imaging demonstrated superior hepatic accumulation of DDN, exhibiting 1.57\u2010 and 2.11\u2010fold greater fluorescence intensity at 240 min post\u2010injection compared to siRNA and tetrahedral framework nucleic acid (tFNA), respectively. In a carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2010induced mouse model, intraperitoneal DDN administration significantly reduced macrophage oxidative burden, ROS generation, and M1 polarization, ultimately mitigating collagen deposition and fibrotic progression. These findings establish DDN as a potent and targeted therapeutic platform for liver fibrosis treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509977","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:07:31Z","timestamp":1761894451000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Dynamic DNA Nano\u2010Antioxidant Targeting Galectin\u20103 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress"],"prefix":"10.1002","volume":"13","author":[{"given":"Mengjia","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Emergency the General Hospital of Tibet Military Command  Lhasa China"},{"name":"Department of Gastroenterology Laboratory of Gastroenterology and Hepatology West China Hospital Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Oral Diseases National Center for Stomatology National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency the General Hospital of Tibet Military Command  Lhasa China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjian","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Emergency the General Hospital of Tibet Military Command  Lhasa China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Emergency the General Hospital of Tibet Military Command  Lhasa China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Physical Examination Center General Hospital of Western Theater Command  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Ci","sequence":"additional","affiliation":[{"name":"Department of Emergency the General Hospital of Tibet Military Command  Lhasa China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-4266","authenticated-orcid":false,"given":"Bowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency the General Hospital of Tibet Military Command  Lhasa China"},{"name":"Department of Gastroenterology Laboratory of Gastroenterology and Hepatology West China Hospital Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Oral Diseases National Center for Stomatology National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01374-X"},{"key":"e_1_2_10_2_1","first-page":"624","volume":"19","author":"Kotsiliti E.","year":"2022","journal-title":"Nat. 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