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A systems toxicology approach to investigate the impacts of the pulmonary surfactant corona formation on graphene oxide toxicity

Grant number: 21/00306-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2022
Effective date (End): February 28, 2026
Field of knowledge:Interdisciplinary Subjects
Principal researcher:Diego Stéfani Teodoro Martinez
Grantee:Marcella Torres Maia
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
Associated research grant:14/50906-9 - INCT 2014: in Functional Complex Materials, AP.TEM

Abstract

Systems toxicology is an approach to connect the molecular and functional changes occurring at different levels of the biological organization to a specific insult suffered by a biological system. The application of this approach in nanosafety research represents the frontier of knowledge; however, it is a scientific area lacking in the Brazilian context so far. The successful translation of systems toxicology to nanosafety practices depends critically upon to the exploration of computational and informatics tools. In this project, we propose to develop a systems toxicology approach for assessing the toxicity of Graphene Oxide (GO) materials; including leveraging strategic research connections with two international leading groups in the UK (Manchester and Birmingham). Indeed, we are advancing to investigate the impacts of the Pulmonary Surfactant (PS) corona on the GO toxicity against pulmonary cells (BEAS-2B and RLE-6TN) for the first time. Corona formation, secretomics and biochemical functional assays will be characterized and analyzed, concerning the identification of the Adverse Outcome Pathways (AOPs). The GO materials that will be studied were synthesized from Brazilian natural graphite and vary only by their lateral dimension: Ultra-Small GO (US-GO) and Large (L-GO). These materials have been investigated as "model samples" by several European groups as part of the Graphene Flagship project. Our preliminary results showed that the PS corona can modulate the cellular response to both GO materials, and that the protein component from the PS presented a higher impact on GO toxicity mitigation than the lipid component. Also, we have identified a size dependent response on the cellular viability and metabolism; besides, we demonstrated the possible EMT (Epithelial-Mesenchymal Transition) induction by both GO materials in the absence of proteins. Thus, in this project, we aim to explain the different contributions of each PS component (proteins and lipids) on GO toxicity mitigation by investigating the GO-PS interactions and their contact with cells; as well as elucidating the role of the GO lateral size. All nanoinformatics tools to be used in this project will be supported by NanoCommons platform and the NanoSolveIT and CompSafeNano H2020-funded projects; to make the project data FAIR (Findable, Accessible, Interoperable, and Reusable). Finally, this project is supporting the development of predictive nanotoxicity methods for graphene-based materials towards safe-by-design, responsible innovation, and regulation. (AU)

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