Innate but not adaptive immunity regulates lung recovery from chronic exposure to graphene oxide nanosheets

Thomas Loret; Luis Augusto Visani de Luna; Alexander Fordham; Atta Arshad; Katharine Barr; Neus Lozano Valdes; Kostas Kostarelos; Cyrill Bussy

doi:10.1002/advs.202104559

Innate but not adaptive immunity regulates lung recovery from chronic exposure to graphene oxide nanosheets

Thomas Loret, Luis Augusto Visani de Luna, Alexander Fordham, Atta Arshad, Katharine Barr, Neus Lozano Valdes, Kostas Kostarelos, Cyrill Bussy

ICN2 Instituto Catala De Nanociencia y Nanotechnologia

Research output: Contribution to journal › Article › peer-review

75 Downloads (Pure)

Abstract

Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both associated to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.

Original language	English
Article number	2104559
Journal	Advanced Science
Volume	9
Issue number	11
DOIs	https://doi.org/10.1002/advs.202104559
Publication status	Published - 15 Feb 2022

Keywords

graphene
safety
toxicity
inhalation
degradation
nanovector

Research Beacons, Institutes and Platforms

Advanced materials
Advanced Materials in Medicine
Digital Futures
Lydia Becker Institute
National Graphene Institute

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/advs.202104559Licence: CC BY

Advanced Science - 2022 - Loret - Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure toFinal published version, 4.43 MBLicence: CC BY

1 Finished
1 Active

CDT in Science and Applications of Graphene and Related Nanomaterial
Grigorieva, I., Burnett, H., Cusworth, E., Deaconu, D., Dumitriu-Iovanescu, A., Kang, Y., Little, J., Rees, E., Selles, F., Shaker, M., Soong, Y., Swindell, J., Tainton, G., Wood, H., Astles, T., Carl, A., Chen, G., Richard De Latour, H., Dowinton, O., Haskell, S., Hills, K., Hoole, C., Huang, Y., Kalsi, T., Powell, L., Quiligotti, K., Rimmer, J., Smith, L., Thornley, W., Yang, J., Young, W., Zhao, M., Al Busaidi, R., Al Ruqeishi, E., Chadha, A., Chen, M., Dennis, G., Dunn, E., Gamblen, E., Gao, Y., Georgantas, Y., Jiang, Z., Karakasidi, A., Mcellistrim, A., Meehan, M., Okwelogu, E., Taylor, M., Wang, W., Xin, B., Castle, C., Clout, P., Dean, S., Fordham, A., Griffin, E., Hardwick, T., Hawkins-Pottier, G., Jones, A., Lewthwaite, K., Monteil, S., Moulsdale, C., Mullan, C., Orts Mercadillo, V., Sanderson, D., Skliueva, I., Skuse, C., Steiner, P., Winstanley, B., Barry, D., Brooks, D., Cai, J., Chen, Y., Chen, C., Draude, A., Emmerson, C., Gavriliuc, V., Greaves, M., Higgins, E., Mcmaster, R., Mcnair, R., O'Brien, C., Peasey, A., Pinter, G., Shao, S., Thomas, D., Thomas, D., Tsim, L. T. B., Wengraf, J., Weston, A., Yu, T., De Libero, H., Chan, K. C., Tan, Y. T. & Thomson, T.
1/04/14 → 31/10/25
Project: Other
Graphene Flagship Core 2 (Division of Pharmacy and Optometry allocation).
Kostarelos, K. & Bussy, C.
1/04/18 → 31/03/20
Project: Research

4 Article
1 Conference contribution

Hazard Assessment of Abraded Thermoplastic Composites Reinforced with Reduced Graphene Oxide
Chortarea, S., Kuru, O. C., Netkueakul, W., Pelin, M., Keshavan, S., Song, Z., Ma, B., Gómes, J., Abalos, E. V., Visani de Luna, L. A., Loret, T., Fordham, A., Drummond, M., Kontis, N., Anagnostopoulos, G., Paterakis, G., Cataldi, P., Tubaro, A., Galiotis, C., Kinloch, I., & 7 othersFadeel, B., Bussy, C., Kostarelos, K., Buerki-Thurnherr, T., Prato, M., Bianco, A. & Wick, P., 5 Aug 2022, In: Journal of Hazardous Materials. 435, 129053.
Research output: Contribution to journal › Article › peer-review

Open Access
File
128 Downloads (Pure)
Lung recovery from DNA damage induced by graphene oxide is dependent on size, dose and inflammation profile
de Luna, L. A. V., Loret, T., Fordham, A., Arshad, A., Drummond, M., Dodd, A., Lozano, N., Kostarelos, K. & Bussy, C., 21 Sept 2022, In: Particle and Fibre Toxicology. 19, 1, 62.
Research output: Contribution to journal › Article › peer-review

Open Access
Pulmonary toxicity of graphene based materials is governed by size-dependant biodegradation and clearance in alveolar phagocytes
Loret, T., Visani de Luna, L. A., Lucarelli, M., Fordham, A., Lozano, N., Bianco, A., Kostarelos, K. & Bussy, C., 12 Sept 2022, Toxicology Letters. supplement 1 ed. Elsevier BV, Vol. 368 . p. S43-S44 1 p.
Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

Open Access

Cite this

@article{870c6f70a8e347c2aabe7b85d3a95e97,

title = "Innate but not adaptive immunity regulates lung recovery from chronic exposure to graphene oxide nanosheets",

abstract = "Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both associated to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.",

keywords = "graphene, safety, toxicity, inhalation, degradation, nanovector",

author = "Thomas Loret and {Visani de Luna}, {Luis Augusto} and Alexander Fordham and Atta Arshad and Katharine Barr and {Lozano Valdes}, Neus and Kostas Kostarelos and Cyrill Bussy",

note = "Funding Information: A.F. and A.A would like to acknowledge studentships co‐funded by the Lloyds Register Foundation funded International Consortium on Nanotechnology (LRF‐ICON) and the UK Research and Innovation Engineering and Physical Sciences Research Council (UKRI‐EPSRC) Centre for Doctoral Training programme Graphene NOWNANO (EP/L01548X/1). This work was also supported by the European Union (EU) 8th Framework Programme for Research and Technological Development, GrapheneFlagship project (H2020‐FET‐GrapheneCore2—#785219 and H2020‐FET‐GrapheneCore3—#881603). The authors also thank Dr. Adrian Esteban Arranz, Dr. Miguel Arellano, Irene Rebollido, and Angeliki Karakasidi for their contributions to the synthesis and characterization of the GO materials used in the present study. Matthew Drummond and Abbie Dodd are acknowledged for their contributions to the tissue collection. In addition, the authors would like to acknowledge the following groups at ICN2 (Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain): Advanced Electronic Materials and Devices led by Prof. Jose Garrido for the AFM and Raman instrumentation and assistance, and Supramolecular NanoChemistry and Materials led by Prof. Daniel Maspoch for the UV–vis equipment and assistance. The ICN2 is funded by the CERCA programme, Generalitat de Catalunya, and is supported by the Severo Ochoa Centres of Excellence programme by the Spanish Research Agency (AEI, grant no. SEV‐2017‐0706). At the Faculty of Biology, Medicine and Health, The University of Manchester, UK, the authors would like to thank the staff from the Biological Services Facility, and the following staff members for expert advice and assistance in using core facility and their provision of technical support services: Peter Walker and Grace Bako (Histology Facility), Dr. Gareth Howell (Flow Cytometry Facility), Claire Morrison (Genomic Facility), Dr. Peter March (Bioimaging Facility), and Dr. N. Hodson (Bio‐AFM Facility). The Bioimaging Facility microscopes used in the present study were purchased with grants from the UKRI Biotechnology and Biological Sciences Research Council (UKRI‐BBSRC), the Wellcome Trust, and the University of Manchester Strategic Fund. Funding Information: A.F. and A.A would like to acknowledge studentships co-funded by the Lloyds Register Foundation funded International Consortium on Nanotechnology (LRF-ICON) and the UK Research and Innovation Engineering and Physical Sciences Research Council (UKRI-EPSRC) Centre for Doctoral Training programme Graphene NOWNANO (EP/L01548X/1). This work was also supported by the European Union (EU) 8th Framework Programme for Research and Technological Development, GrapheneFlagship project (H2020-FET-GrapheneCore2?#785219 and H2020-FET-GrapheneCore3?#881603). The authors also thank Dr. Adrian Esteban Arranz, Dr. Miguel Arellano, Irene Rebollido, and Angeliki Karakasidi for their contributions to the synthesis and characterization of the GO materials used in the present study. Matthew Drummond and Abbie Dodd are acknowledged for their contributions to the tissue collection. In addition, the authors would like to acknowledge the following groups at ICN2 (Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain): Advanced Electronic Materials and Devices led by Prof. Jose Garrido for the AFM and Raman instrumentation and assistance, and Supramolecular NanoChemistry and Materials led by Prof. Daniel Maspoch for the UV?vis equipment and assistance. The ICN2 is funded by the CERCA programme, Generalitat de Catalunya, and is supported by the Severo Ochoa Centres of Excellence programme by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). At the Faculty of Biology, Medicine and Health, The University of Manchester, UK, the authors would like to thank the staff from the Biological Services Facility, and the following staff members for expert advice and assistance in using core facility and their provision of technical support services: Peter Walker and Grace Bako (Histology Facility), Dr. Gareth Howell (Flow Cytometry Facility), Claire Morrison (Genomic Facility), Dr. Peter March (Bioimaging Facility), and Dr. N. Hodson (Bio-AFM Facility). The Bioimaging Facility microscopes used in the present study were purchased with grants from the UKRI Biotechnology and Biological Sciences Research Council (UKRI-BBSRC), the Wellcome Trust, and the University of Manchester Strategic Fund. Publisher Copyright: {\textcopyright} 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.",

year = "2022",

month = feb,

day = "15",

doi = "10.1002/advs.202104559",

language = "English",

volume = "9",

journal = "Advanced Science",

issn = "2198-3844",

publisher = "John Wiley & Sons Ltd",

number = "11",

}

TY - JOUR

T1 - Innate but not adaptive immunity regulates lung recovery from chronic exposure to graphene oxide nanosheets

AU - Loret, Thomas

AU - Visani de Luna, Luis Augusto

AU - Fordham, Alexander

AU - Arshad, Atta

AU - Barr, Katharine

AU - Lozano Valdes, Neus

AU - Kostarelos, Kostas

AU - Bussy, Cyrill

N1 - Funding Information: A.F. and A.A would like to acknowledge studentships co‐funded by the Lloyds Register Foundation funded International Consortium on Nanotechnology (LRF‐ICON) and the UK Research and Innovation Engineering and Physical Sciences Research Council (UKRI‐EPSRC) Centre for Doctoral Training programme Graphene NOWNANO (EP/L01548X/1). This work was also supported by the European Union (EU) 8th Framework Programme for Research and Technological Development, GrapheneFlagship project (H2020‐FET‐GrapheneCore2—#785219 and H2020‐FET‐GrapheneCore3—#881603). The authors also thank Dr. Adrian Esteban Arranz, Dr. Miguel Arellano, Irene Rebollido, and Angeliki Karakasidi for their contributions to the synthesis and characterization of the GO materials used in the present study. Matthew Drummond and Abbie Dodd are acknowledged for their contributions to the tissue collection. In addition, the authors would like to acknowledge the following groups at ICN2 (Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain): Advanced Electronic Materials and Devices led by Prof. Jose Garrido for the AFM and Raman instrumentation and assistance, and Supramolecular NanoChemistry and Materials led by Prof. Daniel Maspoch for the UV–vis equipment and assistance. The ICN2 is funded by the CERCA programme, Generalitat de Catalunya, and is supported by the Severo Ochoa Centres of Excellence programme by the Spanish Research Agency (AEI, grant no. SEV‐2017‐0706). At the Faculty of Biology, Medicine and Health, The University of Manchester, UK, the authors would like to thank the staff from the Biological Services Facility, and the following staff members for expert advice and assistance in using core facility and their provision of technical support services: Peter Walker and Grace Bako (Histology Facility), Dr. Gareth Howell (Flow Cytometry Facility), Claire Morrison (Genomic Facility), Dr. Peter March (Bioimaging Facility), and Dr. N. Hodson (Bio‐AFM Facility). The Bioimaging Facility microscopes used in the present study were purchased with grants from the UKRI Biotechnology and Biological Sciences Research Council (UKRI‐BBSRC), the Wellcome Trust, and the University of Manchester Strategic Fund. Funding Information: A.F. and A.A would like to acknowledge studentships co-funded by the Lloyds Register Foundation funded International Consortium on Nanotechnology (LRF-ICON) and the UK Research and Innovation Engineering and Physical Sciences Research Council (UKRI-EPSRC) Centre for Doctoral Training programme Graphene NOWNANO (EP/L01548X/1). This work was also supported by the European Union (EU) 8th Framework Programme for Research and Technological Development, GrapheneFlagship project (H2020-FET-GrapheneCore2?#785219 and H2020-FET-GrapheneCore3?#881603). The authors also thank Dr. Adrian Esteban Arranz, Dr. Miguel Arellano, Irene Rebollido, and Angeliki Karakasidi for their contributions to the synthesis and characterization of the GO materials used in the present study. Matthew Drummond and Abbie Dodd are acknowledged for their contributions to the tissue collection. In addition, the authors would like to acknowledge the following groups at ICN2 (Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain): Advanced Electronic Materials and Devices led by Prof. Jose Garrido for the AFM and Raman instrumentation and assistance, and Supramolecular NanoChemistry and Materials led by Prof. Daniel Maspoch for the UV?vis equipment and assistance. The ICN2 is funded by the CERCA programme, Generalitat de Catalunya, and is supported by the Severo Ochoa Centres of Excellence programme by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). At the Faculty of Biology, Medicine and Health, The University of Manchester, UK, the authors would like to thank the staff from the Biological Services Facility, and the following staff members for expert advice and assistance in using core facility and their provision of technical support services: Peter Walker and Grace Bako (Histology Facility), Dr. Gareth Howell (Flow Cytometry Facility), Claire Morrison (Genomic Facility), Dr. Peter March (Bioimaging Facility), and Dr. N. Hodson (Bio-AFM Facility). The Bioimaging Facility microscopes used in the present study were purchased with grants from the UKRI Biotechnology and Biological Sciences Research Council (UKRI-BBSRC), the Wellcome Trust, and the University of Manchester Strategic Fund. Publisher Copyright: © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

PY - 2022/2/15

Y1 - 2022/2/15

N2 - Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both associated to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.

AB - Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both associated to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.

KW - graphene

KW - safety

KW - toxicity

KW - inhalation

KW - degradation

KW - nanovector

U2 - 10.1002/advs.202104559

DO - 10.1002/advs.202104559

M3 - Article

SN - 2198-3844

VL - 9

JO - Advanced Science

JF - Advanced Science

IS - 11

M1 - 2104559

ER -

Innate but not adaptive immunity regulates lung recovery from chronic exposure to graphene oxide nanosheets

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

Access to Document

Fingerprint

Projects

CDT in Science and Applications of Graphene and Related Nanomaterial

Graphene Flagship Core 2 (Division of Pharmacy and Optometry allocation).

Research output

Hazard Assessment of Abraded Thermoplastic Composites Reinforced with Reduced Graphene Oxide

Lung recovery from DNA damage induced by graphene oxide is dependent on size, dose and inflammation profile

Pulmonary toxicity of graphene based materials is governed by size-dependant biodegradation and clearance in alveolar phagocytes

Cite this