Single-cell mass cytometry reveals the impact of graphene nanomaterials with human primary immune cells

Kostas Kostarelos; Marco Orecchioni; Davide Bedognetti; Leon Newman; Claudia Fuoco; Filomena Spada; Wouter Hendrickx; Francesco M. Marincola; Francesco Sgarrella; Artur Filipe  Rodrigues; Cécilia Ménard-Moyon; Gianni Cesareni; Alberto Bianco; Lucia Gemma Delogu

doi:10.1038/s41467-017-01015-3

Single-cell mass cytometry reveals the impact of graphene nanomaterials with human primary immune cells

Kostas Kostarelos, Marco Orecchioni, Davide Bedognetti, Leon Newman, Claudia Fuoco, Filomena Spada, Wouter Hendrickx, Francesco M. Marincola, Francesco Sgarrella, Artur Filipe Rodrigues, Cécilia Ménard-Moyon, Gianni Cesareni, Alberto Bianco, Lucia Gemma Delogu

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Abstract

Understanding the biomolecular interactions between graphene nanomaterials and human cells is a prerequisite for the utilization of graphene-based nanomaterials as a diagnostic or therapeutic tool. Currently, the impact of exposure to graphene and its derivative graphene oxide (GO) on the immune system remains elusive. To characterize the complex interactions between graphene nanomaterials and immune cells, we propose an integrative analytical pipeline encompassing the evaluation of molecular and cellular parameters. Single-cell mass cytometry was used to dissect the effects of GO flakes and GO flakes functionalized with amino groups on 15 immune cell populations, interrogating 30 markers at the single-cell level. Next, we integrated single-cell mass cytometry with genome-wide transcriptome analysis and we concluded that the amine groups reduce the perturbations caused by GO on cell metabolism and increase biocompatibility. Moreover, GONH2, but not GO, polarizes T-cell and monocyte activation toward a T helper-1/M1 immune response. These observations support the implementation of nanoscale platforms for immunotherapy, as vaccine carrier and nano-adjuvant. This study describes an innovative approach for the comprehensive analysis of nanomaterial interactions with distinct immune cells, laying the foundation for the incorporation of single-cell mass cytometry for the characterization of nanomaterial-immune cell interactions.

Original language	English
Article number	1109
Pages (from-to)	1109
Journal	Nature Communications
Volume	8
Issue number	1
Early online date	24 Oct 2017
DOIs	https://doi.org/10.1038/s41467-017-01015-3
Publication status	Published - 24 Oct 2017

Keywords

Graphene
2D materials
Nanomedicine
Nanotoxicology
single-cell mass cytometry

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Graphene-Based Disruptive Technologies. MHS Element.
Kostarelos, K. (PI) & Bussy, C. (CoI)
1/04/16 → 31/03/18
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Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment
Fadeel, B., Bussy, C., Merino, S., Vázquez, E., Flahaut, E., Mouchet, F., Evariste, L., Gauthier, L., Koivisto, A. J., Vogel, U., Martin, C., Delogu, L. G., Bürki-Thurnherr, T., Wick, P., Beloin-Saint-Pierre, D., Hischier, R., Pelin, M., Candotto Carniel, F., Tretiach, M. & Cesca, F. & 6 others, Benfenati, F., Scaini, D., Ballerini, L., Kostarelos, K., Prato, M. & Bianco, A., 2018, In: ACS Nano.
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Live Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative Stress-Mediated Cellular Responses
Vranic, S., Rodrigues, A., Buggio, M., Newman, L., White, M., Spiller, D., Bussy, C. (Corresponding) & Kostarelos, K. (Corresponding), 29 Dec 2017, In: ACS Nano. 12, 2, p. 1373 16 p.
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Kostarelos, K., Orecchioni, M., Bedognetti, D., Newman, L., Fuoco, C., Spada, F., Hendrickx, W., Marincola, F. M., Sgarrella, F., Rodrigues, A. F., Ménard-Moyon, C., Cesareni, G., Bianco, A., & Gemma Delogu, L. (2017). Single-cell mass cytometry reveals the impact of graphene nanomaterials with human primary immune cells. Nature Communications, 8(1), 1109. Article 1109. https://doi.org/10.1038/s41467-017-01015-3

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abstract = "Understanding the biomolecular interactions between graphene nanomaterials and human cells is a prerequisite for the utilization of graphene-based nanomaterials as a diagnostic or therapeutic tool. Currently, the impact of exposure to graphene and its derivative graphene oxide (GO) on the immune system remains elusive. To characterize the complex interactions between graphene nanomaterials and immune cells, we propose an integrative analytical pipeline encompassing the evaluation of molecular and cellular parameters. Single-cell mass cytometry was used to dissect the effects of GO flakes and GO flakes functionalized with amino groups on 15 immune cell populations, interrogating 30 markers at the single-cell level. Next, we integrated single-cell mass cytometry with genome-wide transcriptome analysis and we concluded that the amine groups reduce the perturbations caused by GO on cell metabolism and increase biocompatibility. Moreover, GONH2, but not GO, polarizes T-cell and monocyte activation toward a T helper-1/M1 immune response. These observations support the implementation of nanoscale platforms for immunotherapy, as vaccine carrier and nano-adjuvant. This study describes an innovative approach for the comprehensive analysis of nanomaterial interactions with distinct immune cells, laying the foundation for the incorporation of single-cell mass cytometry for the characterization of nanomaterial-immune cell interactions.",

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Kostarelos, K, Orecchioni, M, Bedognetti, D, Newman, L, Fuoco, C, Spada, F, Hendrickx, W, Marincola, FM, Sgarrella, F, Rodrigues, AF, Ménard-Moyon, C, Cesareni, G, Bianco, A & Gemma Delogu, L 2017, 'Single-cell mass cytometry reveals the impact of graphene nanomaterials with human primary immune cells', Nature Communications, vol. 8, no. 1, 1109, pp. 1109. https://doi.org/10.1038/s41467-017-01015-3

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AU - Kostarelos, Kostas

AU - Orecchioni, Marco

AU - Bedognetti, Davide

AU - Newman, Leon

AU - Fuoco, Claudia

AU - Spada, Filomena

AU - Hendrickx, Wouter

AU - Marincola, Francesco M.

AU - Sgarrella, Francesco

AU - Rodrigues, Artur Filipe

AU - Ménard-Moyon, Cécilia

AU - Cesareni, Gianni

AU - Bianco, Alberto

AU - Gemma Delogu, Lucia

PY - 2017/10/24

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N2 - Understanding the biomolecular interactions between graphene nanomaterials and human cells is a prerequisite for the utilization of graphene-based nanomaterials as a diagnostic or therapeutic tool. Currently, the impact of exposure to graphene and its derivative graphene oxide (GO) on the immune system remains elusive. To characterize the complex interactions between graphene nanomaterials and immune cells, we propose an integrative analytical pipeline encompassing the evaluation of molecular and cellular parameters. Single-cell mass cytometry was used to dissect the effects of GO flakes and GO flakes functionalized with amino groups on 15 immune cell populations, interrogating 30 markers at the single-cell level. Next, we integrated single-cell mass cytometry with genome-wide transcriptome analysis and we concluded that the amine groups reduce the perturbations caused by GO on cell metabolism and increase biocompatibility. Moreover, GONH2, but not GO, polarizes T-cell and monocyte activation toward a T helper-1/M1 immune response. These observations support the implementation of nanoscale platforms for immunotherapy, as vaccine carrier and nano-adjuvant. This study describes an innovative approach for the comprehensive analysis of nanomaterial interactions with distinct immune cells, laying the foundation for the incorporation of single-cell mass cytometry for the characterization of nanomaterial-immune cell interactions.

AB - Understanding the biomolecular interactions between graphene nanomaterials and human cells is a prerequisite for the utilization of graphene-based nanomaterials as a diagnostic or therapeutic tool. Currently, the impact of exposure to graphene and its derivative graphene oxide (GO) on the immune system remains elusive. To characterize the complex interactions between graphene nanomaterials and immune cells, we propose an integrative analytical pipeline encompassing the evaluation of molecular and cellular parameters. Single-cell mass cytometry was used to dissect the effects of GO flakes and GO flakes functionalized with amino groups on 15 immune cell populations, interrogating 30 markers at the single-cell level. Next, we integrated single-cell mass cytometry with genome-wide transcriptome analysis and we concluded that the amine groups reduce the perturbations caused by GO on cell metabolism and increase biocompatibility. Moreover, GONH2, but not GO, polarizes T-cell and monocyte activation toward a T helper-1/M1 immune response. These observations support the implementation of nanoscale platforms for immunotherapy, as vaccine carrier and nano-adjuvant. This study describes an innovative approach for the comprehensive analysis of nanomaterial interactions with distinct immune cells, laying the foundation for the incorporation of single-cell mass cytometry for the characterization of nanomaterial-immune cell interactions.

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KW - 2D materials

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KW - Nanotoxicology

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JO - Nature Communications

JF - Nature Communications

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ER -

Single-cell mass cytometry reveals the impact of graphene nanomaterials with human primary immune cells

Abstract

Keywords

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Projects

Graphene-Based Disruptive Technologies. MHS Element.

Research output

Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment

Live Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative Stress-Mediated Cellular Responses

Cite this