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Inspired by the multivalent and cooperative binding of immunoglobulin M (IgM), we developed a biomimetic tandem Y\u2010shaped Sgc8 aptamer\u2010albumin delivery system (TYS\u2010HSA). By grafting two hydrophilic aptamers onto each hydrophobic C18 side chain of poly(maleic anhydride\u2010alt\u20101\u2010octadecene) (C\n                    <jats:sub>18<\/jats:sub>\n                    PMH), we constructed well\u2010defined multivalent aptamer units that self\u2010assembled with human serum albumin (HSA) into an IgM\u2010like ligand corona. Quantitative analysis revealed a high ligand valency of approximately 240 aptamers per TYS\u2010HSA nanoparticle, which, combined with its tandem Y\u2010shaped topology, enables cooperative multivalent recognition. This design achieved high\u2010affinity, stable target recognition while maintaining strong loading capacity for hydrophobic drugs such as paclitaxel. Compared with lower\u2010valency conjugates (MS\u2010HSA, approximately 95 aptamers per nanoparticle), TYS\u2010HSA showed enhanced target binding, prolonged cellular retention, and potent antitumor efficacy after a single intravesical administration in an orthotopic bladder cancer model. With broad drug compatibility and excellent physiological stability, this platform offers a promising and generalizable strategy for the targeted design of albumin\u2010based nanomedicines.\n                  <\/jats:p>","DOI":"10.1002\/smll.202514393","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T09:37:52Z","timestamp":1773913072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bioinspired IgM\u2010Mimetic Polyvalent Aptamer\u2010Albumin Nanoplatform for Targeted Intravesical Therapy of Bladder Cancer"],"prefix":"10.1002","volume":"22","author":[{"given":"Wei","family":"Yao","sequence":"first","affiliation":[{"name":"Punan Branch of Renji Hospital and Institute of Molecular Medicine (IMM) Renji Hospital, School of Medicine Shanghai Jiaotong University Shanghai China"},{"name":"School of Life Sciences Shanghai University  Shanghai 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