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Here, we introduce a supramolecular glycoengineering strategy that bypasses genetic modification. By utilizing a novel metabolic labeling agent, Ac\n                    <jats:sub>4<\/jats:sub>\n                    ManNAda, we successfully install adamantane (Ada, a guest molecule) tags onto macrophage surfaces via native biosynthetic pathways to generate glycoengineered supramolecular macrophages (GSAR\u2010M). This labeling not only significantly enhances recognition of \u03b2\u2010cyclodextrin (\u03b2\u2010CD, a host molecule)\u2010tagged tumor cells via CD\u2010Ada host\u2010guest interactions but also, unexpectedly, acts as an intrinsic activator. It induces a sustained distinct activated state in GSAR\u2010M, characterized by upregulated activation markers and enhanced migratory, phagocytic, and tumoricidal capacities. Furthermore, subsequent LPS stimulation of these cells (termed GSAR\u2010M+) cooperatively amplifies F\u2010actin content and pseudopodia formation, leading to superior tumor cell capture in vitro. In a murine 4T1 breast cancer model, this supramolecular glycoengineering strategy achieves profound tumor growth arrest and effectively remodels the immunosuppressive tumor microenvironment. This study establishes a streamlined, cost\u2010effective, and non\u2010viral engineering paradigm that integrates host\u2010guest recognition with glycometabolic engineering, providing critical insights for the development of next\u2010generation engineered immune cells in adoptive cell therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.76468","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:32:23Z","timestamp":1783945943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Artificial Host\u2010Guest Recognition Directs Glycometabolically Engineered Macrophages to Tumors"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhiqing","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macau Macao SAR China"},{"name":"MoE Frontiers Science Center for Precision Oncology University of Macau  Macau Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Cheng","sequence":"additional","affiliation":[{"name":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Faculty of Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macau Macao SAR China"},{"name":"MoE Frontiers Science Center for Precision Oncology University of Macau  Macau Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Guan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macau Macao SAR China"},{"name":"MoE Frontiers Science Center for Precision Oncology University of Macau  Macau Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huazhong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9628-296X","authenticated-orcid":false,"given":"Qingwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macau Macao SAR China"},{"name":"MoE Frontiers Science Center for Precision Oncology University of Macau  Macau Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-6333","authenticated-orcid":false,"given":"Caixia","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Institute of Molecular Science Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-4241","authenticated-orcid":false,"given":"Ruibing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macau Macao SAR China"},{"name":"MoE Frontiers Science Center for Precision Oncology University of Macau  Macau Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1167"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1711886"},{"key":"e_1_2_9_4_1","first-page":"3322","article-title":"Intent\u2010to\u2010Treat Leukemia Remission by Cd19 Car T Cells of Defined Formulation and Dose in Children and Young Adults","volume":"129","author":"Gardner R. 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