Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization
authors Cicuendez, M; Fernandes, M; Ayan-Varela, M; Oliveira, H; Feito, MJ; Diez-Orejas, R; Paredes, JI; Villar-Rodil, S; Vila, M; Portoles, MT; Duarte, IF
nationality International
journal COLLOIDS AND SURFACES B-BIOINTERFACES
author keywords Graphene oxide; Pristine graphene; Flavin mononucleotide; Macrophages; Inflammatory response; Metabolomics
keywords FEW-LAYER GRAPHENE; SILVER NANOPARTICLES; AQUEOUS DISPERSIONS; CREATINE-KINASE; OXIDE; EXFOLIATION; CHALLENGES; ITACONATE; HEALTH; CELLS
abstract 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-alpha 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.
publisher ELSEVIER
issn 0927-7765
isbn 1873-4367
year published 2020
volume 186
digital object identifier (doi) 10.1016/j.colsurfb.2019.110709
web of science category Biophysics; Chemistry, Physical; Materials Science, Biomaterials
subject category Biophysics; Chemistry; Materials Science
unique article identifier WOS:000518493000027
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journal analysis (jcr 2019):
journal impact factor 4.389
5 year journal impact factor 4.263
category normalized journal impact factor percentile 72.001
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