{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:14Z","timestamp":1790575034394,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Psoriasis is an autoimmune disease characterized primarily by chronic inflammation, with suboptimal clinical therapeutic outcomes. Quercetin, a bio-safe plant secondary metabolite, exerts anti\u2010inflammatory effects by modulating multiple signaling pathways and holds promise as a therapeutic candidate for psoriasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Our preliminary studies demonstrated that silk protein (SF) derived from silkworm cocoons exhibits excellent biocompatibility and can form hydrogels, serving as an ideal drug carrier for skin applications. We loaded quercetin into the SF hydrogel system and systematically investigated the therapeutic efficacy of this composite formulation (QSF) against imiquimod-induced psoriasis models through in vitro and in vivo experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The hydrogel exhibited desirable enzyme-responsive properties. When exposed to an in vitro microenvironment containing 10 nM MMP\u20109, the hydrogel network rapidly disintegrated, achieving a cumulative quercetin release of 58.26% \u00b1 7.64% within 24 h. The enriched quercetin in lesion tissues markedly reduced the positive expression levels of IL\u201017, TNF\u2010\u03b1, and IL\u20101\u03b2, with inhibition rates of 32.14%, 20.25%, and 33.71%, respectively, which effectively interrupted the inflammatory cascade and obviously alleviated skin desquamation and pruritus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, the fabricated QSF hydrogel presents anti\u2010inflammatory and symptomatic relief effects, providing a feasible strategy and experimental basis for the development of novel topical preparations for psoriasis treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1810299","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:35Z","timestamp":1790574275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A smart MMP-9-responsive hydrogel releasing quercetin for psoriasis therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Qinghua","family":"Lan","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Drug Preparation, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, North Henan Medical University","place":["Xinxiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haici","family":"Lan","sequence":"additional","affiliation":[{"name":"College of Food and Health, Zhejiang Agricultural and Forestry University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songmei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1002\/bit.28259","article-title":"A hydrogel-fiber-hydrogel composite scaffold based on silk fibroin with the dual-delivery of oxygen and quercetin","volume":"120","author":"Aleemardani","year":"2023","journal-title":"Biotechnol Bioeng"},{"key":"B2","doi-asserted-by":"publisher","first-page":"114068","DOI":"10.1016\/j.ejmech.2021.114068","article-title":"Quercetin derivatives: drug design, development, and biological activities, a review","volume":"229","author":"Alizadeh","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.jid.2020.09.006","article-title":"MMP-9 mediates cross-talk between neutrophils and endothelial cells in psoriasis","volume":"141","author":"Alves-Filho","year":"2021","journal-title":"J Invest. Dermatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1089\/ped.2019.1137","article-title":"Quercetin improves inflammation, oxidative stress, and impaired wound healing in atopic dermatitis model of human keratinocytes","volume":"33","author":"Beken","year":"2020","journal-title":"Pediatr Allergy Immunol Pulmonol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e52242","DOI":"10.1371\/journal.pone.0052242","article-title":"Cross-study homogeneity of psoriasis gene expression in skin across a large expression range","volume":"8","author":"Bigler","year":"2013","journal-title":"PLoS One"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1021\/acs.jcim.0c01227","article-title":"Toward an understanding of pan-assay interference compounds and promiscuity: a structural perspective on binding modes","volume":"61","author":"Bolz","year":"2021","journal-title":"J. Chem. Inf. Model"},{"key":"B7","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.actbio.2014.09.013","article-title":"Impact of silk biomaterial structure on proteolysis","volume":"11","author":"Brown","year":"2015","journal-title":"Acta Biomater"},{"key":"B8","doi-asserted-by":"publisher","first-page":"9739","DOI":"10.3390\/ijms21249739","article-title":"The roles of matrix metalloproteinases and their inhibitors in human diseases","volume":"21","author":"Cabral-Pacheco","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/(SICI)1097-4636(199901)44:1<53::AID-JBM6>3.0.CO;2-W","article-title":"Synthesis of superporous hydrogels: hydrogels with fast swelling and superabsorbent properties","volume":"44","author":"Chen","year":"2015","journal-title":"Journal of Biomedical Materials Research"},{"key":"B10","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.jid.2020.07.028","article-title":"Neutrophils enhance cutaneous vascular dilation and permeability to aggravate psoriasis by releasing matrix metallopeptidase 9","volume":"141","author":"Chen","year":"2021","journal-title":"J Invest. Dermatol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1084\/jem.20111453","article-title":"IL-1\u03b2 mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells","volume":"209","author":"Coccia","year":"2012","journal-title":"J Exp Med"},{"key":"B12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene expression omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"22103","DOI":"10.1038\/s41598-024-73746-5","article-title":"Integrating protein interaction and pathway crosstalk network reveals a promising therapeutic approach for psoriasis through apoptosis induction","volume":"14","author":"Farahani","year":"2024","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"022004","DOI":"10.1088\/1748-605X\/abb615","article-title":"Crosslinking strategies for silk fibroin hydrogels: promising biomedical materials","volume":"16","author":"Farokhi","year":"2021","journal-title":"Biomed Mater"},{"key":"B15","doi-asserted-by":"publisher","first-page":"14413","DOI":"10.3390\/ijms232214413","article-title":"Synthetic pathways and the therapeutic potential of quercetin and curcumin","volume":"23","author":"Hasan","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"024901","DOI":"10.1063\/5.0226300","article-title":"Nanoscale self-assembly and water retention properties of silk fibroin-riboflavin hydrogel","volume":"162","author":"Kumari","year":"2025","journal-title":"J Chem Phys"},{"key":"B17","doi-asserted-by":"publisher","first-page":"110735","DOI":"10.1016\/j.colsurfb.2019.110735","article-title":"Topical application of silk fibroin-based hydrogel in preventing hypertrophic scars","volume":"186","author":"Li","year":"2020","journal-title":"Colloids Surf B Biointerfaces"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1016\/j.jid.2024.09.012","article-title":"Curing psoriasis","volume":"144","author":"Lwin","year":"2024","journal-title":"J Invest. Dermatol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/978-1-0716-1468-6_15","article-title":"Identification of pan-assay INterference compoundS (PAINS) using an MD-Based protocol","volume":"2315","author":"Magalhes","year":"2021","journal-title":"Methods in Molecular Biology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.colsurfb.2017.10.029","article-title":"Skin-penetrating polymeric nanoparticles incorporated in silk fibroin hydrogel for topical delivery of curcumin to improve its therapeutic effect on psoriasis mouse model","volume":"160","author":"Mao","year":"2017","journal-title":"Colloids Surf B Biointerfaces"},{"key":"B21","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41577-022-00746-9","article-title":"IL-17 and IL-17-producing cells in protection versus pathology","volume":"23","author":"Mills","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/ng.311","article-title":"Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways","volume":"41","author":"Nair","year":"2009","journal-title":"Nat Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1002\/ptr.8426","article-title":"Exploring the therapeutic effects of anisole on psoriasis in mice based on the JAK1\/STAT3 pathway","volume":"39","author":"Ning","year":"2025","journal-title":"Phytother Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.biochi.2024.03.011","article-title":"Matrix metalloproteinase landscape in the imiquimod-induced skin inflammation mouse model","volume":"226","author":"Noddeland","year":"2024","journal-title":"Biochimie"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3849","DOI":"10.3390\/ijms25073849","article-title":"Advancements in regenerative hydrogels in skin wound treatment: a comprehensive review","volume":"25","author":"Olteanu","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5592","DOI":"10.3390\/ijms24065592","article-title":"Impact of obesity on the IL-6 immune marker and Th17 immune cells in C57BL\/6 mice models with imiquimod-induced psoriasis","volume":"24","author":"Park","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"4983","DOI":"10.3390\/ijms22094983","article-title":"Psoriasis: from pathogenesis to pharmacological and nano-technological-based therapeutics","volume":"22","author":"Petit","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"272","DOI":"10.22146\/ijp.4454","article-title":"Validation of Uv-Vis spectrophotometric method to determine drug release of quercetin loaded-nanoemulsion","volume":"34","author":"Putri","year":"2023","journal-title":"Indones. J. Pharm."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/j.drudis.2020.09.023","article-title":"Psoriasis: pathological mechanisms, current pharmacological therapies, and emerging drug delivery systems","volume":"25","author":"Rapalli","year":"2020","journal-title":"Drug Discov Today"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1089262","DOI":"10.3389\/fimmu.2022.1089262","article-title":"Advances in pathogenesis and nanoparticles (NPs)-mediated treatment of psoriasis","volume":"13","author":"Shen","year":"2022","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1177\/039463200601900405","article-title":"VEGF is likely a key factor in the link between inflammation and angiogenesis in psoriasis: results of an immunohistochemical study","volume":"19","author":"Simonetti","year":"2006","journal-title":"Int J Immunopathol Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"32955","DOI":"10.1021\/acsami.8b08119","article-title":"Quercetin inlaid silk fibroin\/hydroxyapatite scaffold promotes enhanced osteogenesis","volume":"10","author":"Song","year":"2018","journal-title":"ACS Appl Mater Interfaces"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.1038\/jid.2012.184","article-title":"Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis","volume":"132","author":"Su\u00e1rez-Fari\u00f1as","year":"2012","journal-title":"J Invest. Dermatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"122991","DOI":"10.1016\/j.lfs.2024.122991","article-title":"Advances in psoriasis research: from pathogenesis to therapeutics","volume":"355","author":"Sugumaran","year":"2024","journal-title":"Life Sci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"eadm7164","DOI":"10.1126\/sciadv.adm7164","article-title":"Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction","volume":"10","author":"Sun","year":"2024","journal-title":"Sci Adv"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e34594","DOI":"10.1371\/journal.pone.0034594","article-title":"Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis","volume":"7","author":"Swindell","year":"2012","journal-title":"PLoS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"106846","DOI":"10.1016\/j.ejps.2024.106846","article-title":"Development of Imiquimod-induced HaCaT-THP-1 co-culture for modeling of psoriasis","volume":"200","author":"V\u00e1radi","year":"2024","journal-title":"Eur J Pharm Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.ejphar.2017.07.040","article-title":"Imiquimod-induced psoriasis-like inflammation in differentiated human keratinocytes: its evaluation using curcumin","volume":"813","author":"Varma","year":"2017","journal-title":"Eur J Pharmacol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"967193","DOI":"10.3389\/fimmu.2022.967193","article-title":"Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis","volume":"13","author":"Wang","year":"2022","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"214571","DOI":"10.1016\/j.bioadv.2025.214571","article-title":"Glycyrrhizic acid-containing Gastrodia elata polysaccharide\/chitosan hydrogel promotes macrophage M2 polarization and accelerates aging skin wound healing","volume":"180","author":"Wang","year":"2025","journal-title":"Biomater Adv"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1007\/s10753-025-02236-1","article-title":"Topical anti-inflammatory effects of quercetin glycosides on atopic dermatitis-like lesions: influence of the glycone type on efficacy and skin absorption","volume":"48","author":"Yang","year":"2025","journal-title":"Inflammation"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e2737","DOI":"10.1371\/journal.pone.0002737","article-title":"Type I interferon: potential therapeutic target for psoriasis?","volume":"3","author":"Yao","year":"2008","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"11719","DOI":"10.7150\/thno.47682","article-title":"Bioinspired biliverdin\/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing","volume":"10","author":"Yao","year":"2020","journal-title":"Theranostics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3206","DOI":"10.3390\/molecules29133206","article-title":"The role of quercetin as a plant-derived bioactive agent in preventive medicine and treatment in skin disorders","volume":"29","author":"Zaborowski","year":"2024","journal-title":"Molecules"},{"key":"B45","doi-asserted-by":"publisher","first-page":"40228","DOI":"10.1021\/acsami.3c07582","article-title":"Cyclodextrin-coordinated liposome-in-gel for transcutaneous quercetin delivery for psoriasis treatment","volume":"15","author":"Zhang","year":"2023","journal-title":"ACS Appl Mater Interfaces"},{"key":"B46","doi-asserted-by":"publisher","first-page":"134351","DOI":"10.1016\/j.ijbiomac.2024.134351","article-title":"Hydrogels comprising oxidized carboxymethyl cellulose and water-soluble chitosan at varied oxidation levels: synthesis, characterization, and adsorptive toward methylene blue","volume":"277","author":"Zhang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10965-025-04519-5","article-title":"Ca2+ induced silk protein hydrogels: structural characteristics, rapid water absorption and anti-compression behavior","volume":"32","author":"Zhang","year":"2025","journal-title":"Journal of Polymer Research"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1810299\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:36Z","timestamp":1790574276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1810299\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":47,"alternative-id":["10.3389\/fphar.2026.1810299"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1810299","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"article-number":"1810299"}}