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Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy.

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Τίτλος: Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy.
Συγγραφείς: Choi H; Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; PHI BIOMED Co., Seocho-gu, Seoul, Korea., Jeong SH; Department of Urology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.; Department of Urology, Seoul National University Hospital, Jongno-gu, Seoul, Korea., Simó C; CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Guipúzcoa, Spain., Bakenecker A; Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Liop J; CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Guipúzcoa, Spain., Lee HS; Department of Urology, Seoul National University Hospital, Jongno-gu, Seoul, Korea., Kim TY; Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea., Kwak C; Department of Urology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea. mdrafael@snu.ac.kr.; Department of Urology, Seoul National University Hospital, Jongno-gu, Seoul, Korea. mdrafael@snu.ac.kr., Koh GY; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Korea. gykoh@kaist.ac.kr., Sánchez S; Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. ssanchez@ibecbarcelona.eu.; Institució Catalana de Recerca i Estudis Avancats (ICREA), Passeig Lluís Companys 23, Barcelona, Spain. ssanchez@ibecbarcelona.eu., Hahn SK; PHI BIOMED Co., Seocho-gu, Seoul, Korea. skhanb@postech.ac.kr.; Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Korea. skhanb@postech.ac.kr.
Πηγή: Nature communications [Nat Commun] 2024 Nov 15; Vol. 15 (1), pp. 9934. Date of Electronic Publication: 2024 Nov 15.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : Nature Pub. Group
Ιατρικοί όροι (MeSH): Urinary Bladder Neoplasms*/therapy , Urinary Bladder Neoplasms*/immunology , Urinary Bladder Neoplasms*/drug therapy , Urinary Bladder Neoplasms*/pathology , Membrane Proteins*/agonists , Membrane Proteins*/metabolism , Membrane Proteins*/genetics , Urease*/metabolism , Immunotherapy*/methods, CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/drug effects ; Programmed Cell Death 1 Receptor/metabolism ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacology ; Urinary Bladder/pathology ; Urinary Bladder/drug effects ; Urinary Bladder/immunology ; BCG Vaccine/therapeutic use ; Animals ; Mice ; Female ; Humans ; Cell Line, Tumor ; Mice, Inbred C57BL ; Administration, Intravesical ; Disease Models, Animal ; STING Protein
Περίληψη: 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.
(© 2024. The Author(s).)
Competing Interests: Competing interests The authors declare no competing interests.
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Substance Nomenclature: 0 (Membrane Proteins)
EC 3.5.1.5 (Urease)
0 (Programmed Cell Death 1 Receptor)
0 (Antibodies, Monoclonal, Humanized)
0 (BCG Vaccine)
0 (Sting1 protein, mouse)
0 (STING Protein)
0 (STING1 protein, human)
DPT0O3T46P (pembrolizumab)
Entry Date(s): Date Created: 20241115 Date Completed: 20241116 Latest Revision: 20260127
Update Code: 20260130
PubMed Central ID: PMC11568179
DOI: 10.1038/s41467-024-54293-z
PMID: 39548120
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2041-1723
DOI:10.1038/s41467-024-54293-z