2. Academic Validation
  3. Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy

Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy

  • Nat Commun. 2024 Nov 15;15(1):9934. doi: 10.1038/s41467-024-54293-z.
Hyunsik Choi # 1 2,  Seung-Hwan Jeong # 3 4,  Cristina Simó 5,  Anna Bakenecker 1,  Jordi Liop 5,  Hye Sun Lee 4,  Tae Yeon Kim 6,  Cheol Kwak 7 8,  Gou Young Koh 9,  Samuel Sánchez 10 11,  Sei Kwang Hahn 12 13
Affiliations

Affiliations

  • 1 Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • 2 PHI BIOMED Co., Seocho-gu, Seoul, Korea.
  • 3 Department of Urology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
  • 4 Department of Urology, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
  • 5 CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Guipúzcoa, Spain.
  • 6 Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea.
  • 7 Department of Urology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea. mdrafael@snu.ac.kr.
  • 8 Department of Urology, Seoul National University Hospital, Jongno-gu, Seoul, Korea. mdrafael@snu.ac.kr.
  • 9 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Korea. gykoh@kaist.ac.kr.
  • 10 Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. ssanchez@ibecbarcelona.eu.
  • 11 Institució Catalana de Recerca i Estudis Avancats (ICREA), Passeig Lluís Companys 23, Barcelona, Spain. ssanchez@ibecbarcelona.eu.
  • 12 PHI BIOMED Co., Seocho-gu, Seoul, Korea. skhanb@postech.ac.kr.
  • 13 Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea. skhanb@postech.ac.kr.
  • # Contributed equally.
PMID: 39548120 DOI: 10.1038/s41467-024-54293-z
Abstract

Most non-muscle invasive bladder cancers have been treated by transurethral resection and following intravesical injection of immunotherapeutic agents. However, the delivery efficiency of therapeutic agents into bladder wall is low due to frequent urination, which leads to the failure of treatment with side effects. Here, we report a urease-powered nanomotor containing the agonist of stimulator of interferon genes (STING) for the efficient activation of immune cells in the bladder wall. After characterization, we perform in vitro motion analysis and assess in vivo swarming behaviors of nanomotors. The intravesical instillation results in the effective penetration and retention of nanomotors in the bladder. In addition, we confirm the anti-tumor effect of nanomotor containing the STING agonist (94.2% of inhibition), with recruitment of CD8+ T cells (11.2-fold compared with PBS) and enhanced anti-tumor immune responses in bladder Cancer model in female mice. Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder Cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder Cancer Immunotherapy.

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