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...

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Autores: 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.
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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dc.title.none.fl_str_mv 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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
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info:eu-repo/semantics/acceptedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/199468
url http://hdl.handle.net/10261/199468
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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RTI2018-100832-B-I00/AEI/10.13039/501100011033
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https://doi.org/10.1016/j.colsurfb.2019.110709

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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)
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spelling 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. 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