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The underlying pathology involves a self-amplifying cycle of reactive oxygen species (ROS) overproduction and macrophage-mediated inflammation, and strategies that concurrently scavenge ROS, reprogram macrophage polarization, and attenuate hepatocyte apoptosis remain lacking. Itaconate (ITA), an endogenous anti-inflammatory metabolite, suffers from poor membrane permeability and lacks intrinsic ROS-scavenging capacity. Herein, we constructed BiOCl@ITA by integrating defect-engineered bismuth oxychloride (BiOCl) with surface-loaded ITA. Oxygen vacancy engineering confers intrinsic superoxide dismutase (SOD)- and catalase (CAT)-mimicking activities under stimulus-free conditions. BiOCl@ITA showed rapid accumulation in the liver within 0.5 h after intraperitoneal administration and was efficiently internalized by both hepatocytes and macrophages in vitro. Moreover, BiOCl@ITA virtually eliminated intracellular ROS and attenuated APAP-induced hepatocyte injury, while also reprogramming LPS-stimulated macrophages from M1 toward an M2 phenotype, consistently outperforming free ITA across all endpoints. In a murine APAP-induced ALI model, BiOCl@ITA-treated mice showed near-complete thermal recovery by 24 h, accompanied by substantially reduced serum hepatic injury markers and attenuated histopathological damage. Hepatic molecular and tissue-level analyses further demonstrated restoration of antioxidant defenses, favorable regulation of BAX\/BCL-2 expression, and sustained M1-to-M2 macrophage polarization in vivo. These findings demonstrate that BiOCl@ITA synergistically integrates catalytic ROS detoxification with ITA-mediated macrophage reprogramming, offering a promising therapeutic approach for APAP-induced acute liver injury.<\/jats:p>","DOI":"10.1021\/acsami.6c08667","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:02:01Z","timestamp":1787036521000},"page":"46022-46042","source":"Crossref","is-referenced-by-count":0,"title":["Rapidly Liver-Accumulating BiOCl@ITA Nanozyme for Synergistic ROS Scavenging and Macrophage Reprogramming in APAP-Induced Liver Injury"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9671-7331","authenticated-orcid":true,"given":"Junli","family":"Huang","sequence":"first","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Huang","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Huang","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baomin","family":"Fang","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Bi","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shitong","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangzhou First People\u2019s Hospital, Guangzhou Medical University , , ,","place":["Guangzhou, China, 510180"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henghai","family":"Su","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Academy of Sciences , , ,","place":["Nanning, Guangxi, China, 530007"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"issue":"26","key":"2026101216070607500_cit1","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1056\/NEJMra1208937","article-title":"Acute Liver Failure","volume":"369","author":"Bernal","year":"2013","journal-title":"N. 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