title: Molecular and Genomic Impact of Large and Small Lateral Dimension Graphene Oxide Sheets on Human Immune Cells from Healthy Donors.
abstract: Graphene oxide (GO) is attracting great interest in biomedical sciences. The impact of GO on immune cells is one fundamental area of study that is often overlooked, but critical in terms of clinical translation. This work investigates the effects of two types of thoroughly characterized GO sheets, different in their lateral dimension, on human peripheral immune cells provided from healthy donors using a wide range of assays. After evaluation of cell viability, the gene expression was analyzed, following GO exposure on 84 genes related to innate and adaptive immune responses. Exposure to GO small sheets was found to have a more significant impact on immune cells compared to GO large sheets, reflected in the upregulation of critical genes implicated in immune responses and the release of cytokines IL1β and TNFα. These findings were further confirmed by whole-genome microarray analysis of the impact of small GO sheets on T cells and monocytes. Activation in both cell types was underlined by the overexpression of genes such as CXCL10 and receptor CXCR3. Significant energy-dependent pathway modulation was identified. These findings can potentially pave the foundations for further design of graphene that can be used for immune modulation applications, for example in cancer immunotherapy.
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100, Sassari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Orecchioni
authors.affiliation: Nanomedicine Lab, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Dhifaf A
authors.initials: DA
authors.lastname: Jasim
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100, Sassari, Italy.|Heath-E-Solutions, Rotterdam, 3016, DL, The Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Pescatori
authors.affiliation: Department of Clinical Medicine and Experimental Oncology, University of Sassari, 07100, Sassari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Manetti
authors.affiliation: Department of Biomedical Science, University of Sassari, 07100, Sassari, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fozza
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100, Sassari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sgarrella
authors.affiliation: Research Branch, Sidra Medical and Research Centre, Doha, Qatar.
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratorie d'Immunopathologie et Chimie Thérapeutique, 67000, Strasbourg, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Nanomedicine Lab, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100, Sassari, Italy.
authors.forename: Lucia Gemma
authors.initials: LG
authors.lastname: Delogu
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D023281:Genomics; D006108:Graphite / Q000494:pharmacology*; D006262:Health; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014019:Tissue Donors
chemical_list: D016207:Cytokines; D006108:Graphite
keywords: carbon nanomaterials; immunotherapy; immunotoxicity; microarray; nanomedicine