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 w...

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Autores: Choi, Hyunsik, Jeong, Seung Hwan, Simó, Cristina, Bakenecker, Anna, Liop, Jordi, Lee, Hye Sun, Kim, Tae Yeon, Kwak, Cheol, Koh, Gou Young, Sánchez Ordóñez, Samuel, Hahn, Sei Kwang
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/220757
Acceso en línea:https://hdl.handle.net/2445/220757
Access Level:acceso abierto
Palabra clave:Immunoteràpia
Càncer de bufeta
Immunotheraphy
Bladder cancer
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spelling Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapyChoi, HyunsikJeong, Seung HwanSimó, CristinaBakenecker, AnnaLiop, JordiLee, Hye SunKim, Tae YeonKwak, CheolKoh, Gou YoungSánchez Ordóñez, SamuelHahn, Sei KwangImmunoteràpiaCàncer de bufetaImmunotheraphyBladder cancerMost 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.Springer Nature2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/220757Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-024-54293-zNature Communications, 2024, vol. 15https://doi.org/10.1038/s41467-024-54293-zcc-by-nc-nd (c) Choi, Hyunsik et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2207572026-05-27T06:46:51Z
dc.title.none.fl_str_mv Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
title Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
spellingShingle Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
Choi, Hyunsik
Immunoteràpia
Càncer de bufeta
Immunotheraphy
Bladder cancer
title_short Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
title_full Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
title_fullStr Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
title_full_unstemmed Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
title_sort Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy
dc.creator.none.fl_str_mv Choi, Hyunsik
Jeong, Seung Hwan
Simó, Cristina
Bakenecker, Anna
Liop, Jordi
Lee, Hye Sun
Kim, Tae Yeon
Kwak, Cheol
Koh, Gou Young
Sánchez Ordóñez, Samuel
Hahn, Sei Kwang
author Choi, Hyunsik
author_facet Choi, Hyunsik
Jeong, Seung Hwan
Simó, Cristina
Bakenecker, Anna
Liop, Jordi
Lee, Hye Sun
Kim, Tae Yeon
Kwak, Cheol
Koh, Gou Young
Sánchez Ordóñez, Samuel
Hahn, Sei Kwang
author_role author
author2 Jeong, Seung Hwan
Simó, Cristina
Bakenecker, Anna
Liop, Jordi
Lee, Hye Sun
Kim, Tae Yeon
Kwak, Cheol
Koh, Gou Young
Sánchez Ordóñez, Samuel
Hahn, Sei Kwang
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Immunoteràpia
Càncer de bufeta
Immunotheraphy
Bladder cancer
topic Immunoteràpia
Càncer de bufeta
Immunotheraphy
Bladder cancer
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/220757
url https://hdl.handle.net/2445/220757
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-024-54293-z
Nature Communications, 2024, vol. 15
https://doi.org/10.1038/s41467-024-54293-z
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Choi, Hyunsik et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Choi, Hyunsik et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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