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However, traditional hormone replacement therapy (HRT) only restores the thyroid hormone concentration in serum, not in the brain, which leads to damage to hippocampal synaptic plasticity in the brain that can't be repaired. In addition, there is also oxidative damage, which makes the symptoms of encephalopathy still persist, and indicates the need for a new collaborative treatment approach for hypothyroid encephalopathy disease. In this study, a synergistic therapy system is constructed using Zn\u2010Curcumin\u2010based metal\u2013organic framework (medi\u2010MOF\u20101) with levothyroxine\u20104 is loaded (LT4@medi\u2010MOF\u20101). The results showed that LT4@medi\u2010MOF\u20101 can efficiently deliver thyroid hormone into the brain, co\u2010release hormones and curcumin, and restore thyroid hormone levels in the brain. Furthermore, the curcumin can repair oxidative damage, and hormones and curcumin can work together to enhance synaptic plasticity. In the hypothyroidism rat model, LT4@medi\u2010MOF\u20101 exhibits excellent capacity in ameliorating spatial learning and memory deficits, and shows the potential of a hypothyroid encephalopathy agent for cooperative treatment.<\/jats:p>","DOI":"10.1002\/smll.202505935","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:23:39Z","timestamp":1751516619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Using Levothyroxin\u2010Loaded Zn\u2010Curcumin MOF to Achieve Collaborative Treatment of Hypothyroidic Encephalopathy through Reducing Oxidative Stress and Re\u2010Building Synaptic Plasticity"],"prefix":"10.1002","volume":"21","author":[{"given":"Jinxin","family":"Zhu","sequence":"first","affiliation":[{"name":"Thyroid Department General Surgery Center First Hospital of Jilin University Jilin University  Changchun 130031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education and Faculty of Chemistry Northeast Normal University  Changchun 130024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enpeng","family":"Xi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education and Faculty of Chemistry Northeast Normal University  Changchun 130024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education and Faculty of Chemistry Northeast Normal University  Changchun 130024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuming","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education and Faculty of Chemistry Northeast Normal University  Changchun 130024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"International Curriculum Center High School Attached to Northeast Normal University Northeast Normal University  Changchun 130024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-1544","authenticated-orcid":false,"given":"Nan","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education and Faculty of Chemistry Northeast Normal University  Changchun 130024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Dong","sequence":"additional","affiliation":[{"name":"Thyroid Department General Surgery Center First Hospital of Jilin University Jilin University  Changchun 130031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Thyroid Department General Surgery Center First Hospital of Jilin University Jilin University  Changchun 130031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2007.09.015"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2019.101319"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/M23-1593"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14020198"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.041"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2021.12.003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145706006481"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.59717\/j.xinn-med.2023.100026"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-007-0208-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-023-03460-1"},{"key":"e_1_2_7_11_1","first-page":"510","volume":"18","author":"Lempri\u00e8re S.","year":"2022","journal-title":"Nat. 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