Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy

Hyunsik Choi, Seung-hwan Jeong, Cristina Simó, Anna Bakenecker, Jordi Liop, Hye Sun Lee, Tae Yeon Kim, Cheol Kwak (), Gou Young Koh (), Samuel Sánchez () and Sei Kwang Hahn ()
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Hyunsik Choi: The Barcelona Institute of Science and Technology (BIST)
Seung-hwan Jeong: Seoul National University College of Medicine
Cristina Simó: Basque Research and Technology Alliance (BRTA)
Anna Bakenecker: The Barcelona Institute of Science and Technology (BIST)
Jordi Liop: Basque Research and Technology Alliance (BRTA)
Hye Sun Lee: Seoul National University Hospital
Tae Yeon Kim: Pohang University of Science and Technology (POSTECH)
Cheol Kwak: Seoul National University College of Medicine
Gou Young Koh: Korea Advanced Institute of Science and Technology (KAIST)
Samuel Sánchez: The Barcelona Institute of Science and Technology (BIST)
Sei Kwang Hahn: PHI BIOMED Co.

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54293-z

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