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This study developed APTES\u2010functionalized spiky titanium dioxide nanoparticles (ASNPs) loaded with botulinum toxin A (ASNP@BA), which is coated with P407\/HA (HP) thermosensitive gel to treat OAB. Spiky nanoparticles exhibited a spiky nanostructure and were APTES\u2010functionalized to exhibit enhanced drug\u2010loading capacity. The optimal HP gel changed from liquid to gel near body temperature. In vitro, ASNPs enter cells via MYH9\u2010mediated endocytosis. The expression of ZO\u20101 and E\u2010cadherin proteins, along with changes in TEER, indicates that ASNPs entering cells do not compromise the integrity of the bladder barrier. In vivo, ASNP@HP showed excellent biocompatibility. Following bladder instillation of ASNP@HP, no significant toxicity was observed in major organs. The bladder barrier integrity was not significantly compromised. In a rat model, pretreatment of the bladder with ASNP@HPBA significantly reduced the excessive contraction induced by acetic acid, markedly reducing the intercontraction interval decline to 41.83% \u00b1 17.78% compared to controls (\u223c75%) and free BTX\u2010A (71.72%). The downregulation of SNAP\u201025 and SNAP\u201023 in the ASNP@HPBA group demonstrated successful targeted delivery and bioactivity. This platform combines macromolecular drug delivery with effective therapeutic efficacy and safety profile, representing a promising strategy for the treatment of OAB.<\/jats:p>","DOI":"10.1002\/adhm.202505843","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:11:20Z","timestamp":1774595480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spiky Nanoparticle\u2010Gel Composite for Efficient Intravesical Botulinum Toxin A Delivery and Treatment of Overactive Bladder"],"prefix":"10.1002","volume":"15","author":[{"given":"Yongheng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Urology Qilu Hospital of Shandong University Shandong University  Jinan Shandong China"},{"name":"Department of Urology China Rehabilitation Research Center  Beijing China"},{"name":"University of Health and Rehabilitation Sciences  Qingdao Shandong China"},{"name":"China 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