{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:44:04Z","timestamp":1779147844939,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFB3805902"],"award-info":[{"award-number":["2022YFB3805902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22077118"],"award-info":[{"award-number":["22077118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"\u201c111\u201d project","doi-asserted-by":"crossref","award":["B18012"],"award-info":[{"award-number":["B18012"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of Jilin Province","award":["20210101353JC"],"award-info":[{"award-number":["20210101353JC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Polyphenols like dihydroquercetin, rutin, and rifampicin show promise for Alzheimer\u2019s disease (AD) therapy due to their ability to inhibit amyloid-\u03b2 (A\u03b2) aggregation and reduce reactive oxygen species (ROS), garnering significant recent interest. However, their efficacy is substantially diminished because excess metal ions present in amyloid plaques can chelate these compounds. Therefore, reshaping the metal microenvironment in the patient\u2019s brain is particularly important for the therapeutic effect of AD. To address the above issues, we have constructed a composite system formed by NH2-MIL-101(Fe) (MOF), dihydroquercetin (DHQ), and D-penicillamine (D-pen). Due to the lack of \u03c0-\u03c0 interaction and the low adsorption energy between D-pen\/MOF, the release order and speed of D-pen was much faster than DHQ, thus achieving metal microenvironment regulation and ensuring the therapeutic effect of DHQ. In a 5 \u00d7 FAD transgenic mouse model, DD@MOF treated and improved spatial learning and memory deficits. Therefore, the DD@MOF based on polyphenolic compounds provides a potential research direction for intervention in Alzheimer\u2019s disease through chelating copper ions and antioxidant properties.<\/jats:p>","DOI":"10.3390\/molecules31010111","type":"journal-article","created":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T23:54:36Z","timestamp":1766966076000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["D-Penicillamine\/Dihydroquercetin Dual-Loaded Metal\u2013Organic Framework as a Microenvironment Copper Regulator for Enhancing the Therapeutic Efficacy of Polyphenolic Antioxidant in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"31","author":[{"given":"Xuhan","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licong","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiling","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6399-1398","authenticated-orcid":false,"given":"Enpeng","family":"Xi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8845-5546","authenticated-orcid":false,"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pardridge, W.M. 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