TY - JOUR
T1 - First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses
AU - Andrews, Jack P.M.
AU - Joshi, Shruti S.
AU - Tzolos, Evangelos
AU - Syed, Maaz B.
AU - Cuthbert, Hayley
AU - Crica, Livia E.
AU - Lozano, Neus
AU - Okwelogu, Emmanuel
AU - Raftis, Jennifer B.
AU - Bruce, Lorraine
AU - Poland, Craig A.
AU - Duffin, Rodger
AU - Fokkens, Paul H.B.
AU - Boere, A. John F.
AU - Leseman, Daan L.A.C.
AU - Megson, Ian L.
AU - Whitfield, Phil D.
AU - Ziegler, Kerstin
AU - Tammireddy, Seshu
AU - Hadjidemetriou, Marilena
AU - Bussy, Cyrill
AU - Cassee, Flemming R.
AU - Newby, David E.
AU - Kostarelos, Kostas
AU - Miller, Mark R.
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
Funding Information:
We thank all the staff at the Edinburgh Wellcome Trust Clinical Research Facility and M. Doris for their assistance with the participant study days. We also thank J. MacLeod for performing the screening visit exercise tests and the NHS Royal Infirmary of Edinburgh staff for the clinical biochemistry measurements. We also thank F. Howie and K. Wilson for their assistance in measuring TNF-α and IL-6, and the members of the University of Edinburgh SuRF histology laboratories for the processing and imaging of Badimon strips. We gratefully acknowledge the assistance of the SSC2b medical students (J. Garcia Fernandez, L. Buijs, S. Henry and N. Cameron) who participated in the initial data processing. We thank the staff at the Manchester Mass Spectrometry Facility, FTIR Facility, EM Facility and Bio-AFM Facility for assistance and advice regarding instrumentation. The University of Manchester Bioimaging Facility microscopes (EM, AFM) used in the present study were purchased with grants from the UK Research and Innovation (UKRI) Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the University of Manchester Strategic Fund. We also acknowledge the UK Research and Innovation (UKRI) Engineering and Physical Sciences Research Council (EPSRC) Harwell XPS facility based at Cardiff University for the provision of X-ray photoelectron spectrometric data. Finally, we thank all the volunteers taking part in the study, which would not have been possible without them.
This work was funded by the British Heart Foundation (grant numberSP/15/8/31575, M.R.M.), a UKRI and Engineering and Physical Sciences Research Council EPSRC 2D-Health Programme Grant (UKRI-EPSRC EP/P00119X/1) and the University of Manchester Strategic Fund studentship (both K.K.). The ICN2 is funded by the CERCA programme/Generalitat de Catalunya and has been supported by the Severo Ochoa Centres of Excellence programme (grant number SEV-2017-0706) and is currently supported by the Severo Ochoa Centres of Excellence programme, grant number CEX2021-001214-S, both funded by MCIN/AEI/10.13039.501100011033. S.S.J. and D.E.N. are supported by the British Heart Foundation (grant numbers FS/CRTF/20/24087, CH/09/002, RG/05/003, RG/10/9/28286, PG/03/017/15071, RG/16/10/32375 and RE/18/5/34216, all D.E.N.). D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA).
PY - 2024/2/16
Y1 - 2024/2/16
N2 - Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m−3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.
AB - Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m−3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.
UR - https://www.scopus.com/pages/publications/85185101591
UR - https://www.scopus.com/pages/publications/85185101591#tab=citedBy
U2 - 10.1038/s41565-023-01572-3
DO - 10.1038/s41565-023-01572-3
M3 - Article
C2 - 38366225
AN - SCOPUS:85185101591
SN - 1748-3387
VL - 19
SP - 705
EP - 714
JO - Nature Nanotechnology
JF - Nature Nanotechnology
ER -