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While surface engineering can enhance tissue accumulation, strategies that preserve biocompatibility and enable scalable production remain limited. Here, we introduce boiling as a simple thermal processing approach that structurally reconfigures ginger extracellular vesicles (GEVs) into functionally enhanced, thermally reassembled GEVs (T-GEVs). The surface architecture of T-GEVs is enriched with key vesicle trafficking regulators, including V-type proton adenosine triphosphatase subunit G, ARF1, and \u03b2-adaptin-like protein. This specific composition drives their tissue-specific accumulation in the intestine and liver and potentiates clathrin-dependent cellular uptake in intestinal cells by 8.57-fold. Beyond superior intrinsic anti-inflammatory activity through NLRP3 inflammasome suppression, T-GEVs function as an efficient oral delivery platform. When loaded with tumor necrosis factor-\u03b1 (TNF-\u03b1) small interfering RNA, they enable a synergistic therapy that combines innate anti-inflammatory activity with targeted gene silencing of TNF-\u03b1, showing potent efficacy in colitis. Our findings position boiling as a natural strategy for enhancing the bioactivity and targeted oral delivery potential of GEVs.<\/jats:p>","DOI":"10.34133\/research.1377","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T09:07:55Z","timestamp":1783501675000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":1,"title":["Thermally Induced Reassembly of Ginger Extracellular Vesicles for Oral Therapy of Intestinal Inflammation"],"prefix":"10.34133","volume":"9","author":[{"given":"Linhai","family":"Hou","sequence":"first","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."},{"name":"Engineering Research Center of Bio-Process, Ministry of Education, School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, \rChina Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-2344","authenticated-orcid":true,"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."},{"name":"Engineering Research Center of Bio-Process, Ministry of Education, School of Food and Biological Engineering, \rHefei University of Technology, Hefei 230009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-025-00922-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.0675"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.jfca.2021.103879","article-title":"Raw versus cooked food matching: Nutrient intake using the 2015\/16 Kenya Integrated Household Budget Survey","volume":"102","author":"Moltedo A","year":"2021","unstructured":"Moltedo A, Jim\u00e9nez S, \u00c1lvarez-S\u00e1nchez C, Manyani T, Ramos MP, Custodio E. 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