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Herein, two isoreticular covalent organic frameworks (Se\u2010COF and Se\u2010BCOF) are developed by Schiff\u2010base condensation of emissive tetraphenylethylene and diselenide\u2010bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3\/ASC\/Caspase\u20101 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up\u2010regulation of nuclear Nrf\u20102 and its downstream gene Mn\u2010SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3\/ASC\/Caspase\u20101 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug\u2010induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug\u2010induced liver injury.<\/jats:p>","DOI":"10.1002\/smll.202402656","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:15:21Z","timestamp":1723612521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Redox\u2010Responsive AIEgen Diselenide\u2010Covalent Organic Framework Composites Targeting Hepatic Macrophages for Treatment of Drug\u2010induced Liver Injury"],"prefix":"10.1002","volume":"20","author":[{"given":"Jialu","family":"Zhuang","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyou","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Anhui Medical University Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-2777","authenticated-orcid":false,"given":"Guiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2021.10.035"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100545"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2023.2223959"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.04.019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00966-y"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01014-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140196"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.01.025"},{"key":"e_1_2_10_6_1","first-page":"305","volume":"119","author":"Imaeda A. 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