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However, existing radioembolic microspheres face limitations, such as single size selection, poor elasticity, lack of theranostic integration, and insufficient stability, which limit their clinical application in TARE. In this study, polydopamine@chitosan (PDA@CS) microspheres featuring a micro\u2010nano composite structure are fabricated by a facile microfluidic method. These microspheres stably chelate Lu\n                    <jats:sup>3+<\/jats:sup>\n                    (forming\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010PDA@CS microspheres) through catechol\u2010metal coordination via the phenolic hydroxyl groups of PDA nanoparticles (PDA NPs). The compact structure of the microspheres with uniformly incorporated PDA NPs ensures radioactive stability through dual retention mechanisms: chemical retention via phenolic hydroxyl groups and physical retention by microsphere matrix. These microspheres exhibit uniform and precisely tunable sizes, good biocompatibility, appropriate elasticity, structural stability, and integrated theranostic capabilities. Key properties of PDA@CS microspheres, including morphology, elasticity, loading capacity and binding stability of Lu\n                    <jats:sup>3+<\/jats:sup>\n                    , can be regulated by adjusting the PDA NPs concentration in the internal fluid phase. In vivo TARE studies in rat models demonstrate that\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010PDA@CS microspheres not only retain well within the hepatic artery, but also effectively inhibit tumor growth and metastasis while maintaining excellent biosafety. The proposed radioembolic microspheres show significant potential as an innovative radioembolic agent for primary liver cancer.\n                  <\/jats:p>","DOI":"10.1002\/smll.73838","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:45:31Z","timestamp":1779353131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<sup>177<\/sup>\n                    Lu\u2010Loaded Composite Microspheres with Micro\/Nano\u2010Structure for Radioembolization Therapy of Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"22","author":[{"given":"Ling\u2010Yun","family":"Guo","sequence":"first","affiliation":[{"name":"School of Chemical Engineering Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Shan","family":"Yang","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital 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