Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets

The glioblastoma (GBM) microenvironment is immunologically “cold” and marked by immunosuppressive components that limit the effectiveness of current immunotherapies. Tumor-associated macrophages and microglia (TAMMs) exist in an immunosuppressive state and contribute to this “coldness,” promoting tu...

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Autores: Stylianou, Maria, Kisby, Thomas, Despotopoulou, Despoina, Parker, Helen, Thawley, Alexandra, Arashvand, Kiana, Lozano, Neus, MacDonald, Andrew S., Kostarelos, Kostas
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/388526
Acceso en línea:http://hdl.handle.net/10261/388526
https://api.elsevier.com/content/abstract/scopus_id/85214327242
Access Level:acceso abierto
Palabra clave:2D materials
Glioblastoma, cancer nanomedicine
Graphene oxide
Immunomodulation
Immunotherapy
Macrophage reprogramming
Resiquimod
TAMMs
Tumor-associated macrophages/microglia
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spelling Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheetsStylianou, MariaKisby, ThomasDespotopoulou, DespoinaParker, HelenThawley, AlexandraArashvand, KianaLozano, NeusMacDonald, Andrew S.Kostarelos, Kostas2D materialsGlioblastoma, cancer nanomedicineGraphene oxideImmunomodulationImmunotherapyMacrophage reprogrammingResiquimodTAMMsTumor-associated macrophages/microgliaThe glioblastoma (GBM) microenvironment is immunologically “cold” and marked by immunosuppressive components that limit the effectiveness of current immunotherapies. Tumor-associated macrophages and microglia (TAMMs) exist in an immunosuppressive state and contribute to this “coldness,” promoting tumor progression and resistance to therapy. Traditional macrophage reprogramming strategies face challenges in delivery and retention of agents within the GBM microenvironment, leading to limited clinical success. This study investigated whether two-dimensional graphene oxide (GO) nanosheets can enhance the delivery of a TLR7/8 agonist (R848) to TAMMs. GO effectively delivered R848, enhancing TAMM reprogramming from an M2-like to an M1-like state in vitro. In a syngeneic mouse model, GO:R848 treatment significantly increased M1-like markers (MHCII, CD86, and TNF-α), reduced M2-like markers (ARG1 and YM1), increased T cell infiltration, and inhibited tumor progression. These findings demonstrate that GO nanosheets can improve the selective local delivery of immunomodulatory agents and alter the immune landscape of GBM.M.S., T.K., A.T., K.A., H.P., A.S.M., and K.K. would like to acknowledge the United Kingdom Research and Innovation (UKRI) Engineering and Physical Sciences Research Council (EPSRC) 2D-Health Programme Grant (EP/P00119X/1) for financial support. T.K. and K.K. would also like to acknowledge the UKRI (EPSRC) for an International Centre-to-Centre grant (EP/S030719/1). The ICN2 is funded by the CERCA programme, Generalitat de Catalunya and is supported by the Severo Ochoa Centres of Excellence program by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). The authors would like to acknowledge the ICN2 Advanced Electronic Materials and Devices Group (Prof. Jose A. Garrido) for access to the AFM instrumentation. The authors would like to thank Kate Hills and Abbie Dodd for their assistance with surgeries and sample processing. The authors would also like to thank the Bioimaging core facility, Biological Services facility, Flow Cytometry facility, and Histology core facility at the University of Manchester for technical support and access to equipment.With funding from the Spanish government through the "Severo Ochoa Centre of Excelence" accreditation (SEV-2017-0706)Peer reviewedElsevierCell PressUK Research and InnovationEngineering and Physical Sciences Research Council (UK)Generalitat de CatalunyaAgencia Estatal de Investigación (España)Kostarelos, Kostas [0000-0002-2224-6672]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/388526https://api.elsevier.com/content/abstract/scopus_id/85214327242reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//SEV-2017-0706The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.xcrp.2024.102342https://doi.org/10.1016/j.xcrp.2024.102342Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3885262026-05-22T06:33:51Z
dc.title.none.fl_str_mv Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
title Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
spellingShingle Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
Stylianou, Maria
2D materials
Glioblastoma, cancer nanomedicine
Graphene oxide
Immunomodulation
Immunotherapy
Macrophage reprogramming
Resiquimod
TAMMs
Tumor-associated macrophages/microglia
title_short Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
title_full Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
title_fullStr Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
title_full_unstemmed Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
title_sort Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
dc.creator.none.fl_str_mv Stylianou, Maria
Kisby, Thomas
Despotopoulou, Despoina
Parker, Helen
Thawley, Alexandra
Arashvand, Kiana
Lozano, Neus
MacDonald, Andrew S.
Kostarelos, Kostas
author Stylianou, Maria
author_facet Stylianou, Maria
Kisby, Thomas
Despotopoulou, Despoina
Parker, Helen
Thawley, Alexandra
Arashvand, Kiana
Lozano, Neus
MacDonald, Andrew S.
Kostarelos, Kostas
author_role author
author2 Kisby, Thomas
Despotopoulou, Despoina
Parker, Helen
Thawley, Alexandra
Arashvand, Kiana
Lozano, Neus
MacDonald, Andrew S.
Kostarelos, Kostas
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv UK Research and Innovation
Engineering and Physical Sciences Research Council (UK)
Generalitat de Catalunya
Agencia Estatal de Investigación (España)
Kostarelos, Kostas [0000-0002-2224-6672]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv 2D materials
Glioblastoma, cancer nanomedicine
Graphene oxide
Immunomodulation
Immunotherapy
Macrophage reprogramming
Resiquimod
TAMMs
Tumor-associated macrophages/microglia
topic 2D materials
Glioblastoma, cancer nanomedicine
Graphene oxide
Immunomodulation
Immunotherapy
Macrophage reprogramming
Resiquimod
TAMMs
Tumor-associated macrophages/microglia
description The glioblastoma (GBM) microenvironment is immunologically “cold” and marked by immunosuppressive components that limit the effectiveness of current immunotherapies. Tumor-associated macrophages and microglia (TAMMs) exist in an immunosuppressive state and contribute to this “coldness,” promoting tumor progression and resistance to therapy. Traditional macrophage reprogramming strategies face challenges in delivery and retention of agents within the GBM microenvironment, leading to limited clinical success. This study investigated whether two-dimensional graphene oxide (GO) nanosheets can enhance the delivery of a TLR7/8 agonist (R848) to TAMMs. GO effectively delivered R848, enhancing TAMM reprogramming from an M2-like to an M1-like state in vitro. In a syngeneic mouse model, GO:R848 treatment significantly increased M1-like markers (MHCII, CD86, and TNF-α), reduced M2-like markers (ARG1 and YM1), increased T cell infiltration, and inhibited tumor progression. These findings demonstrate that GO nanosheets can improve the selective local delivery of immunomodulatory agents and alter the immune landscape of GBM.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/388526
https://api.elsevier.com/content/abstract/scopus_id/85214327242
url http://hdl.handle.net/10261/388526
https://api.elsevier.com/content/abstract/scopus_id/85214327242
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//SEV-2017-0706
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.xcrp.2024.102342
https://doi.org/10.1016/j.xcrp.2024.102342
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
Cell Press
publisher.none.fl_str_mv Elsevier
Cell Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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