Multiparametric profiling of engineered nanomaterials : unmasking the surface coating effect
Gallud, Aucrey (Karolinska Institutet (Estocolm, Suècia). Institute of Environmental Medicine)
Delaval, Mathilde (Karolinska Institutet (Estocolm, Suècia). Institute of Environmental Medicine)
Kinaret, Pia (Tampere University. Faculty of Medicine and Health Technology)
Marwah, Veer Singh (University of Helsinki. Institute of Biotechnology)
Fortino, Vittorio (University of Eastern Finland. Institute of Biomedicine)
Ytterberg, Jimmy (Karolinska Institutet (Estocolm, Suècia). Department of Medical Biochemistry and Biophysics)
Zubarev, Roman (Karolinska Institutet (Estocolm, Suècia). Department of Medical Biochemistry and Biophysics)
Skoog, Tiina (Karolinska Institutet (Estocolm, Suècia). Department of Biosciences and Nutrition)
Kere, Juha (Karolinska Institutet (Estocolm, Suècia). Department of Biosciences and Nutrition)
Correia, Manuel (Technical University of Denmark. National Food Institute)
Loeschner, Katrin (Technical University of Denmark. National Food Institute)
Al-Ahmady, Zahraa (Nottingham Trent University. School of Science & Technology)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)
Ruiz, Jaime (Université de Bordeaux)
Astruc, Didier (Université de Bordeaux)
Monopoli, Marco (Royal College of Surgeons in Ireland. Department of Pharmaceutical & Medicinal Chemistry)
Handy, Richard D (University of Plymouth. School of Biological & Marine Sciences)
Moya, Sergio (CIC biomaGUNE. Soft Matter Nanotechnology Laboratory)
Savolainen, Kai (Finnish Institute of Occupational Health)
Alenius, Harri (University of Helsinki. Institute of Biotechnology)
Greco, Dario (University of Helsinki. Institute of Biotechnology)
Fadeel, Bengt (Karolinska Institutet (Estocolm, Suècia). Institute of Environmental Medicine)

Data:	2020
Resum:	Despite considerable efforts, the properties that drive the cytotoxicity of engineered nanomaterials (ENMs) remain poorly understood. Here, the authors inverstigate a panel of 31 ENMs with different core chemistries and a variety of surface modifications using conventional in vitro assays coupled with omics-based approaches. Cytotoxicity screening and multiplex-based cytokine profiling reveals a good concordance between primary human monocyte-derived macrophages and the human monocyte-like cell line THP-1. Proteomics analysis following a low-dose exposure of cells suggests a nonspecific stress response to ENMs, while microarray-based profiling reveals significant changes in gene expression as a function of both surface modification and core chemistry. Pathway analysis highlights that the ENMs with cationic surfaces that are shown to elicit cytotoxicity downregulated DNA replication and cell cycle responses, while inflammatory responses are upregulated. These findings are validated using cell-based assays. Notably, certain small, PEGylated ENMs are found to be noncytotoxic yet they induce transcriptional responses reminiscent of viruses. In sum, using a multiparametric approach, it is shown that surface chemistry is a key determinant of cellular responses to ENMs. The data also reveal that cytotoxicity, determined by conventional in vitro assays, does not necessarily correlate with transcriptional effects of ENMs.
Ajuts:	European Commission 309329
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Immunotoxicity ; Nanomaterials ; Nanotoxicology ; Proteomics ; Transcriptomics
Publicat a:	Advanced science, Vol. 7, Núm. 22 (November 2020) , p. 2002221, ISSN 2198-3844

DOI: 10.1002/advs.202002221
PMID: 33240770

18 p, 12.4 MB

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