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To address this, we develop an innovative carrier\u2010free hydrogel (BBR\u2010MF gel) via molecular co\u2010assembly of berberine (BBR) and mangiferin (MF). This self\u2010assembled system forms a stable, shear\u2010thinning, and self\u2010healing network driven by\n                    <jats:italic>\u03c0\u2013\u03c0<\/jats:italic>\n                    stacking and hydrogen bonding, enabling injectable administration and enhances skin retention for synergistic drug delivery. In an imiquimod\u2010induced murine psoriasis model, topical application of the BBR\u2010MF gel significantly alleviate clinical and histopathological symptoms, outperforming individual BBR or MF treatments. Transcriptomic analysis revealed potent downregulation of the IL\u201017 and NF\u2010\u03baB signaling pathways. Mechanistically, the gel directly inhibits neutrophil extracellular trap formation (NETosis) and, by altering the neutrophil secretome, subsequently attenuates the activation of NF\u2010\u03baB and STAT3 pathways in keratinocytes, thereby disrupting a critical pathogenic immune\u2010epidermal crosstalk. The hydrogel exhibit excellent biocompatibility both in vitro and in vivo. This work presents a safe and effective self\u2010assembled nanoplatform that not only augments the synergistic efficacy of natural products but also unveiled a multimodal mechanism targeting NETosis and inflammatory signaling, offering a promising translational strategy for psoriasis and related inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71373","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:28:41Z","timestamp":1782127721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Berberine\u2010Mangiferin Self\u2010Assembled Carrier\u2010Free Hydrogel Suppresses NETosis for Augmented Psoriasis Treatment"],"prefix":"10.1002","volume":"15","author":[{"given":"Wen\u2010Bin","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica State Key Laboratory of Advanced Drug Delivery and Release Systems Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences) Key Lab for Rare &amp; Uncommon Diseases of Shandong Province Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Jia","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica State Key Laboratory of Advanced Drug Delivery and Release Systems Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences) Key Lab for Rare &amp; Uncommon Diseases of Shandong Province Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of 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