Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
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<sup>+</sup> 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.
Authors
- Hye Sun Lee (ORCID: https://orcid.org/0000-0001-6328-6948)
- Jordi Llop (ORCID: https://orcid.org/0000-0002-0821-9838)
- Sei Kwang Hahn (ORCID: https://orcid.org/0000-0002-7718-6259)
- Anna C. Bakenecker (ORCID: https://orcid.org/0000-0002-9708-3476)
- Cristina Simó (ORCID: https://orcid.org/0000-0002-5980-9379)
- Samuel Sánchez (ORCID: https://orcid.org/0000-0001-9713-9997)
- Seung‐hwan Jeong (ORCID: https://orcid.org/0000-0002-8076-3643)
- Cheol Kwak (ORCID: https://orcid.org/0000-0002-1987-2111)
- Gou Young Koh (ORCID: https://orcid.org/0000-0002-1231-1485)
- Tae‐Yeon Kim (ORCID: https://orcid.org/0000-0003-4743-6023)
- Hyunsik Choi
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Pohang University of Science and Technology (KR)
- Seoul National University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- New Generation University College (ET)
- Seoul National University Hospital (KR)
- CIC biomaGUNE (ES)
- Seoil University (KR)
- National University College (PR)
- Institute for Bioengineering of Catalonia (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1038/s41467-024-54293-z
- Citations
- 47
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 11.30
Funders
- Centres de Recerca de Catalunya
- Korea Medical Device Development Fund
- European Commission
- National Research Foundation
- Generalitat de Catalunya
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona
- Agencia Estatal de Investigación