{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:43:54Z","timestamp":1792680234259,"version":"4.5.0"},"reference-count":76,"publisher":"Wiley","issue":"59","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ\u2010MSX1224"],"award-info":[{"award-number":["CSTB2024NSCQ\u2010MSX1224"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["82425015"],"award-info":[{"award-number":["82425015"]}],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA1209400"],"award-info":[{"award-number":["2024YFA1209400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFA0915000"],"award-info":[{"award-number":["2023YFA0915000"]}],"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":["22374043"],"award-info":[{"award-number":["22374043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92475101"],"award-info":[{"award-number":["92475101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171102"],"award-info":[{"award-number":["82171102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mucosal inflammatory disorders such as dry eye disease (DED) and inflammatory bowel disease (IBD), driven by TNF\u2010\u03b1\u2010mediated immune\u2010epithelial crosstalk, remain therapeutically challenging.\u00a0Conventional inhibitors often suffer from poor mucosal permeability and transient efficacy with 1:1 binding. Although extracellular protein degradation (eTPD) technologies can eliminate pathogenic proteins, most of them operate stoichiometrically, limiting dosage efficiency and durability. Here, we report a receptor\u2010mediated endolysosomal recycling chimera (RECYC) platform that enables catalytic, recyclable degradation of TNF\u2010\u03b1 with multiple turnovers, achieving sustained suppression of mucosal inflammation. RECYC integrates a pH\u2010responsive peptide that binds TNF\u2010\u03b1 at physiological pH and releases it in acidic endosomes, with a CI\u2010M6PR\u2010targeting aptamer that remains pH\u2010stable to drive continuous recycling. The anti\u2010TNF\u2010\u03b1 RECYC achieved efficient uptake and recyclable clearance of extracellular TNF\u2010\u03b1 across conjunctival and colonic epithelial cells and macrophages, achieving superstoichiometric TNF\u2010\u03b1 clearance with up to 7.5 catalytic turnovers. The \u223c30\u00a0kDa RECYC exhibited superior tissue penetration in murine cornea and colon compared to inhibitory antibodies. In murine DED and IBD models, RECYC restored ocular surface homeostasis and reduced colon inflammation with low\u2010dose, infrequent administration. Human corneal limbus organoids further confirmed prolonged anti\u2010inflammatory activity. Together, RECYC establishes a modular, recyclable eTPD platform for sustained treatment of TNF\u2010\u03b1\u2010driven mucosal inflammation.<\/jats:p>","DOI":"10.1002\/adma.74818","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:38:46Z","timestamp":1787974726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Receptor\u2010Mediated Endolysosomal Recycling Chimera Enables Catalytic TNF\u2010\u03b1 Degradation for Sustained Treatment of Mucosal Inflammation"],"prefix":"10.1002","volume":"38","author":[{"given":"Wenxue","family":"Xie","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology and Nanomedicine State Key Laboratory of Chemo and Biosensing Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology College of Chemistry and Chemical Engineering Hunan University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3718-8838","authenticated-orcid":false,"given":"Yuqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Eye &amp; ENT Hospital State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-0178","authenticated-orcid":false,"given":"Xichen","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Eye &amp; ENT Hospital State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Nanomedicine State Key Laboratory of Chemo and Biosensing Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology College of Chemistry and Chemical Engineering Hunan University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Nanomedicine State Key Laboratory of Chemo and Biosensing Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology College of Chemistry and Chemical Engineering Hunan University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Nanomedicine State Key Laboratory of Chemo and Biosensing Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology College of Chemistry and Chemical Engineering Hunan University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujian","family":"Wen","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Nanomedicine State Key Laboratory of Chemo and Biosensing Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology College of Chemistry and Chemical Engineering Hunan University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiteng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Eye &amp; ENT Hospital State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Eye &amp; ENT Hospital State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1847-7432","authenticated-orcid":false,"given":"Bo","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Mianyang 404 Hospital  Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9719-4889","authenticated-orcid":false,"given":"Xujiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Eye &amp; ENT Hospital State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-8343","authenticated-orcid":false,"given":"Hang","family":"Xing","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Nanomedicine State Key Laboratory of Chemo and Biosensing Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology College of Chemistry and Chemical Engineering Hunan University  Changsha China"},{"name":"Research Institute of Hunan University in Chongqing  Chongqing China"},{"name":"Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases\uff1bShanghai Engineering Research Center of Synthetic Immunology Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-633X","authenticated-orcid":false,"given":"Jiaxu","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Eye &amp; ENT Hospital State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Fudan University  Shanghai China"},{"name":"NHC Key Laboratory of Myopia and Related Eye Diseases  Shanghai China"},{"name":"Department of Ophthalmology Children's Hospital of Fudan University National Pediatric Medical Center of China  Shanghai China"},{"name":"Department of Ophthalmology Jinjiang Second Hospital  Fujian Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-025-01305-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00551-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10209"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000792\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.169"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.08.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12\u201011515"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2023.08.004"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31803dcda2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31826a80ea"},{"key":"e_1_2_10_13_1","first-page":"2983","article-title":"Tanfanercept Ophthalmic Solution, a Topical TNF Inhibitor, Significantly Improved Tear Volume in Subjects With Dry Eye Disease in a Phase 3 Study (VELOS\u20103)","volume":"65","author":"Kim Y.","year":"2024","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10792\u2010022\u201002245\u20101"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.37039\/1982.8551.20220003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4274\/tjo.48379"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010023\u201000833\u2010z"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11\u20107871"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.02.024"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.08.013"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102545\u20109"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010021\u201000770\u20101"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010022\u201001456\u20102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2024.01.002"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202425123"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12392"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202300694"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-025-01924-1"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201052685\u20109"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c08521"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201046130\u20100"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c08886"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202218106"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202102170"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202402522"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c15047"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005235\u20106"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007947\u20103"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202417942"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c10010"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010024\u201001801\u20103"},{"key":"e_1_2_10_42_1","first-page":"24506","article-title":"Covalent LYTAC Enabled by DNA Aptamers for Immune Checkpoint Degradation Therapy","volume":"145","author":"Li Y.","year":"2023","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056648\u20106"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c11823"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrp.2025.102778"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf6249"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1691"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201052975\u20102"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2525047123"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2016.10.005"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107118"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b02572"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac300708r"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.3c03775"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3067"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5CC04628A"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08\u20102372"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2024.0101"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD015070.pub2"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001757\u20109"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101328"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01849"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010018"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.02.003"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161375"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1362336"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13704"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S366836"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/1740\u20102557\u20102\u20106"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.3341\/kjo.2016.30.4.302"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102019\u2010320022"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010025\u201001703\u20104"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201002004\u2010x"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000966\u20104"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201002043\u20104"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2018.10.023"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.05.039"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.74818","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.74818","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.74818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:20:13Z","timestamp":1792678813000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.74818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":76,"journal-issue":{"issue":"59","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/adma.74818"],"URL":"https:\/\/doi.org\/10.1002\/adma.74818","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"2025-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e74818"}}