Spiky Nanoparticle-Gel Composite for Efficient Intravesical Botulinum Toxin A Delivery and Treatment of Overactive Bladder

  • Adv Healthc Mater. 2026 Jun;15(21):e05843. doi: 10.1002/adhm.202505843.
Yongheng Zhou  1  2  3  4  5 ,  Qinggang Liu  6 ,  Linna Wang  7 ,  Haoyu Sun  8 ,  Yixi Liu  2  4  9 ,  Tianyu Xiang  2  4  9 ,  Meikai Zhu  1  2  3  4  5 ,  Xin Liu  2  4  9 ,  Tao Liu  2  4  9 ,  Huiling Cong  2  4  9 ,  Limin Liao  1  2  3  4  5  9
Affiliations
  • 1. Department of Urology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
  • 2. Department of Urology, China Rehabilitation Research Center, Beijing, China.
  • 3. University of Health and Rehabilitation Sciences, Qingdao, Shandong, China.
  • 4. China Rehabilitation Science Institute, Beijing, China.
  • 5. Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.
  • 6. Department of Urology, Qingdao Municipal Hospital, Qingdao, China.
  • 7. Lanzhou Biotechnique Development Co., Ltd, Lanzhou, Gansu, China.
  • 8. Department of Urology, The Second Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • 9. School of Rehabilitation, Capital Medical University, Beijing, China.
PMID: 41889245 DOI: 10.1002/adhm.202505843
Abstract

Overactive bladder (OAB) is a symptomatic disease that is difficult to treat. This study developed APTES-functionalized 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-functionalized to exhibit enhanced drug-loading capacity. The optimal HP gel changed from liquid to gel near body temperature. In vitro, ASNPs enter cells via MYH9-mediated endocytosis. The expression of ZO-1 and E-cadherin 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% ± 17.78% compared to controls (∼75%) and free BTX-A (71.72%). The downregulation of SNAP-25 and SNAP-23 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.

Keywords
botulinum toxin A; drug delivery; overactive bladder; spiky nanoparticle.
Products