Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy

• Published in: Nature communications 2024-11, Vol.15 (1), p.9934-16, Article 9934
• Main Authors: Choi, Hyunsik, Jeong, Seung-hwan, Simó, Cristina, Bakenecker, Anna, Liop, Jordi, Lee, Hye Sun, Kim, Tae Yeon, Kwak, Cheol, Koh, Gou Young, Sánchez, Samuel, Hahn, Sei Kwang
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/21; 13/31; 14; 14/19; 14/28; 59; 59/5; 59/78; 631/61/350; 631/67/589/1336; 692/699/67/1059/2325; Administration, Intravesical; Agonists; Animals; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Anticancer properties; Bacillus Calmette-Guerin vaccine; BCG; BCG Vaccine - therapeutic use; Biodegradation; Bladder; Bladder cancer; Cancer; Cancer immunotherapy; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell Line, Tumor; Disease Models, Animal; Drug delivery; Drug development; Female; Humanities and Social Sciences; Humans; Immune system; Immunotherapy; Immunotherapy - methods; Lymphocytes; Lymphocytes T; Membrane Proteins - agonists; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Micromotors; multidisciplinary; Nanotechnology devices; PD-1 protein; Pembrolizumab; Pharmacology; Programmed Cell Death 1 Receptor - metabolism; Science; Science (multidisciplinary); Side effects; Stimulators; Swarming; Transcription activation; Tumors; Urease; Urease - metabolism; Urinary Bladder - drug effects; Urinary Bladder - immunology; Urinary Bladder - pathology; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - immunology; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - therapy; Urination
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54293-z

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. Self-propelling micro/nanomotors represent a therapeutic option for drug delivery. Here the authors report the design and characterization of a biodegradable urease-powered nanomotor containing STING agonist, promoting anti-tumor immune responses in bladder cancer models.