Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization
The preparation of graphene-based nanomaterials (GBNs) with appropriate stability and biocompatibility is crucial for their use in biomedical applications. In this work, three GBNs differing in size and/or functionalization have been synthetized and characterized, and their in vitro biological effec...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/199468 |
| Acceso en línea: | http://hdl.handle.net/10261/199468 |
| Access Level: | acceso abierto |
| Palabra clave: | Graphene oxide Pristine graphene Flavin mononucleotide Macrophages Inflammatory response Metabolomics |
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Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| title |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| spellingShingle |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization Cicuéndez, Mónica Graphene oxide Pristine graphene Flavin mononucleotide Macrophages Inflammatory response Metabolomics |
| title_short |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| title_full |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| title_fullStr |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| title_full_unstemmed |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| title_sort |
Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization |
| dc.creator.none.fl_str_mv |
Cicuéndez, Mónica Fernandes, Márcia Ayán-Varela, Miguel Oliveira, Helena Feito, María José Díez-Orejas, Rosalía Paredes Nachón, Juan Ignacio Villar Rodil, Silvia Vila, Mercedes Portolés, María Teresa Duarte, Iola F. |
| author |
Cicuéndez, Mónica |
| author_facet |
Cicuéndez, Mónica Fernandes, Márcia Ayán-Varela, Miguel Oliveira, Helena Feito, María José Díez-Orejas, Rosalía Paredes Nachón, Juan Ignacio Villar Rodil, Silvia Vila, Mercedes Portolés, María Teresa Duarte, Iola F. |
| author_role |
author |
| author2 |
Fernandes, Márcia Ayán-Varela, Miguel Oliveira, Helena Feito, María José Díez-Orejas, Rosalía Paredes Nachón, Juan Ignacio Villar Rodil, Silvia Vila, Mercedes Portolés, María Teresa Duarte, Iola F. |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Economía y Competitividad (España) Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) Principado de Asturias Villar Rodil, Silvia [0000-0002-5832-9971] Paredes Nachón, Juan Ignacio [0000-0002-0044-9153] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Graphene oxide Pristine graphene Flavin mononucleotide Macrophages Inflammatory response Metabolomics |
| topic |
Graphene oxide Pristine graphene Flavin mononucleotide Macrophages Inflammatory response Metabolomics |
| description |
The preparation of graphene-based nanomaterials (GBNs) with appropriate stability and biocompatibility is crucial for their use in biomedical applications. In this work, three GBNs differing in size and/or functionalization have been synthetized and characterized, and their in vitro biological effects were compared. Pegylated graphene oxide (GO-PEG, 200–500 nm) and flavin mononucleotide-stabilized pristine graphene with two different sizes (PG-FMN, 200–400 nm and 100–200 nm) were administered to macrophages, chosen as cellular model due to their key role in the processing of foreign materials and the regulation of inflammatory responses. The results showed that cellular uptake of GBNs was mainly influenced by their lateral size, while the inflammatory potential depended also on the type of functionalization. PG-FMN nanomaterials (both sizes) triggered significantly higher nitric oxide (NO) release, together with some intracellular metabolic changes, similar to those induced by the prototypical inflammatory stimulus LPS. NMR metabolomics revealed that macrophages incubated with smaller PG-FMN displayed increased levels of succinate, itaconate, phosphocholine and phosphocreatine, together with decreased creatine content. The latter two variations were also detected in cells incubated with larger PG-FMN nanosheets. On the other hand, GO-PEG induced a decrease in the inflammatory metabolite succinate and a few other changes distinct from those seen in LPS-stimulated macrophages. Assessment of TNF-α secretion and macrophage surface markers (CD80 and CD206) further corroborated the low inflammatory potential of GO-PEG. Overall, these findings revealed distinct phenotypic and metabolic responses of macrophages to different GBNs, which inform on their immunomodulatory activity and may contribute to guide their therapeutic applications. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2020 2020 |
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info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Postprint info:eu-repo/semantics/acceptedVersion |
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article |
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acceptedVersion |
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http://hdl.handle.net/10261/199468 |
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http://hdl.handle.net/10261/199468 |
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Inglés |
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Inglés |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Elsevier |
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Elsevier |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalizationCicuéndez, MónicaFernandes, MárciaAyán-Varela, MiguelOliveira, HelenaFeito, María JoséDíez-Orejas, RosalíaParedes Nachón, Juan IgnacioVillar Rodil, SilviaVila, MercedesPortolés, María TeresaDuarte, Iola F.Graphene oxidePristine grapheneFlavin mononucleotideMacrophagesInflammatory responseMetabolomicsThe preparation of graphene-based nanomaterials (GBNs) with appropriate stability and biocompatibility is crucial for their use in biomedical applications. In this work, three GBNs differing in size and/or functionalization have been synthetized and characterized, and their in vitro biological effects were compared. Pegylated graphene oxide (GO-PEG, 200–500 nm) and flavin mononucleotide-stabilized pristine graphene with two different sizes (PG-FMN, 200–400 nm and 100–200 nm) were administered to macrophages, chosen as cellular model due to their key role in the processing of foreign materials and the regulation of inflammatory responses. The results showed that cellular uptake of GBNs was mainly influenced by their lateral size, while the inflammatory potential depended also on the type of functionalization. PG-FMN nanomaterials (both sizes) triggered significantly higher nitric oxide (NO) release, together with some intracellular metabolic changes, similar to those induced by the prototypical inflammatory stimulus LPS. NMR metabolomics revealed that macrophages incubated with smaller PG-FMN displayed increased levels of succinate, itaconate, phosphocholine and phosphocreatine, together with decreased creatine content. The latter two variations were also detected in cells incubated with larger PG-FMN nanosheets. On the other hand, GO-PEG induced a decrease in the inflammatory metabolite succinate and a few other changes distinct from those seen in LPS-stimulated macrophages. Assessment of TNF-α secretion and macrophage surface markers (CD80 and CD206) further corroborated the low inflammatory potential of GO-PEG. Overall, these findings revealed distinct phenotypic and metabolic responses of macrophages to different GBNs, which inform on their immunomodulatory activity and may contribute to guide their therapeutic applications.This work was developed in the scope of the projects CICECO-Aveiro Institute of Materials, FCT Ref. UID/CTM/50011/2019, and CESAM, FCT Ref. UID/AMB/50017/2019, financed by national funds through FCT/MCTES, Portugal. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). Further acknowledgments are due to Bruker BioSpinGmbH and the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No 739572 - The Discoveries CTR. I.F.D. and H.O. acknowledge FCT/MCTES for research contracts under the Programs ‘Investigador FCT’ and Stimulus to Scientific Employment (CEECIND/04050/2017), respectively, and M.C. acknowledges the FCT-awarded research grant SFRH/BPD/101468/2014. This research was also supported by the Spanish Ministerio de Economía y Competitividad (MAT2016-75611-R AEI/FEDER, UE). M.A.-V., S.V.-R. and J.I.P. acknowledge financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) and the European Regional Development Fund (ERDF) through project MAT2015-69844-R, and from the Spanish Ministerio de Ciencia, Innovación y Universidades, the Spanish Agencia Estatal de Investigación and ERDF, through project RTI2018-100832-B-I00. Partial funding by Plan de Ciencia, Tecnología e Innovación (PCTI) 2013-2017 del Principado de Asturias and ERDF (project IDI/2018/000233) is also acknowledged.Peer reviewedElsevierMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Principado de AsturiasVillar Rodil, Silvia [0000-0002-5832-9971]Paredes Nachón, Juan Ignacio [0000-0002-0044-9153]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/199468reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MAT2016-75611-RRTI2018-100832-B-I00/AEI/10.13039/501100011033info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MAT2015-69844-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-100832-B-I00https://doi.org/10.1016/j.colsurfb.2019.110709Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1994682026-05-22T06:33:51Z |
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