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Leveraging host\u2013guest recognition, a series of macrocycle\u2010incorporated polymers is synthesized and engineered a new class of supramolecular microspheres, which feature precisely tunable components, including host molecules, guest cargoes, and polymer components, as well as customizable morphologies, while enabling cost\u2010effective, large\u2010scale production. Following systematic validation of the host\u2013guest recognition between \u03b2\u2010cyclodextrin (\u03b2\u2010CD) and lanreotide, we developed supramolecular microspheres (LAN@S\u2010CPMs) that achieve a drug loading capacity and release duration approximately twice that of conventional microspheres, effectively curbing the disease progression of acromegaly. Beyond sustained release, porous supramolecular microspheres (S\u2010P[5]PMs\u2010p) fabricated from the pillar[5]arene (P[5])\u2010incorporated polymer exhibit exceptional efficiency in spermine adsorption, while mineralized supramolecular microspheres (SORA@S\u2010CPMs\u2010p@CaCO\n                    <jats:sub>3<\/jats:sub>\n                    ) loaded with sorafeinib (SORA) are successfully employed in embolization therapy, achieving more complete vascular occlusion compared to non\u2010mineralized microspheres. The modular design of supramolecular microspheres and facile scalability in production offer a transformative platform to overcome the multifaceted challenges currently faced by microsphere\u2010based delivery systems.\n                  <\/jats:p>","DOI":"10.1002\/smtd.202501053","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T11:02:56Z","timestamp":1756810976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Supramolecular Microspheres Fabricated from Macrocycle\u2010Incorporated Polymers and Their Biomedical Applications Based on Host\u2010Guest Recognition"],"prefix":"10.1002","volume":"9","author":[{"given":"Yangfan","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Department of Chemistry Tsinghua University  Beijing 100084 P. R. 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