Size‐Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe‐by‐Design. Issue 12 (7th May 2020)

• Record Type: Journal Article
• Authors: Rodrigues, Artur Filipe; Newman, Leon; Jasim, Dhifaf; Mukherjee, Sourav P.; Wang, Jun; Vacchi, Isabella A.; Ménard‐Moyon, Cécilia; Bianco, Alberto; Fadeel, Bengt; Kostarelos, Kostas; Bussy, Cyrill
• Is Part Of: Advanced science. Volume 7:Issue 12(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-07
• Subjects: graphene oxide -- inflammation -- lung -- macrophages -- mice -- RNA sequencing; Science -- Periodicals; 505
• DOI: 10.1002/advs.201903200
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Safety assessment of graphene‐based materials (GBMs) including graphene oxide (GO) is essential for their safe use across many sectors of society. In particular, the link between specific material properties and biological effects needs to be further elucidated. Here, the effects of lateral dimensions of GO sheets in acute and chronic pulmonary responses after single intranasal instillation in mice are compared. Micrometer‐sized GO induces stronger pulmonary inflammation than nanometer‐sized GO, despite reduced translocation to the lungs. Genome‐wide RNA sequencing also reveals distinct size‐dependent effects of GO, in agreement with the histopathological results. Although large GO, but not the smallest GO, triggers the formation of granulomas that persists for up to 90 days, no pulmonary fibrosis is observed. These latter results can be partly explained by Raman imaging, which evidences the progressive biotransformation of GO into less graphitic structures. The findings demonstrate that lateral dimensions play a fundamental role in the pulmonary response to GO, and suggest that airborne exposure to micrometer‐sized GO should be avoided in the production plant or applications, where aerosolized dispersions are likely to occur. These results are important toward the implementation of a safer‐by‐design approach for GBM products and applications, for the benefit of workers and end‐users. Abstract : Bulk transcriptomics in lungs of mice after pulmonary exposure to graphene oxide (GO) sheets of varying lateral dimensions reveals size‐dependent adverse effects and provides valuable information for safer‐by‐design production of GO sheet suspension. Analysis of histopathology, material fate and bioaccumulation, cell recruitment, and cytokine secretion confirms more adverse effects with micrometric GO than with nanometric GO.