Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization



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Cicuéndez, Mónica and Fernándes, Márcia and Ayán-Varela, Miguel and Oliveira, Helena and Feito Castellano, María José and Díez Orejas, Rosalía and Paredes, Juan I. and Villar-Rodil, Silvia and Vila, Mercedes and Portolés Pérez, María Teresa and Duarte, Iola F. (2020) Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization. Colloids and Surfaces B: Biointerfaces, 186 (110709). pp. 1-10. ISSN 0927-7765

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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.

Item Type:Article
Uncontrolled Keywords:Graphene oxide; Pristine graphene; Flavin mononucleotide; Macrophages; Inflammatory response; Metabolomics
Subjects:Sciences > Chemistry
Medical sciences > Biology > Biochemistry
ID Code:60469
Deposited On:22 Sep 2020 10:45
Last Modified:22 Sep 2020 10:45

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