In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy

Jonathan Noonan, Steven Asiala, Gianluca Grassia, Neil MacRitchie, Kirsten Gracie, Jake Carson, Matthew Moores, Mark Girolami, Angela Bradshaw, Thomas J. Guzik, Gavin R. Meehan, Hannah Scales, James M. Brewer, Iain B. McInnes, Naveed Sattar, Karen Faulds, Paul Garside, Duncan Graham, Pasquale Maffia

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis. The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi parameter molecular imaging technologies have been established to date. Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS).
Methods: A series of antibody-functionalized gold nanoprobes (BFNP) were designed containing unique Raman signals in order to detect intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin using SERS.
Results: SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin in vitro on human endothelial cells and ex vivo in human coronary arteries. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes.
Conclusion: This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation in vivo and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.
LanguageEnglish
Pages6195-6209
Number of pages15
JournalTheranostics
Volume8
Issue number22
Early online date29 Nov 2018
DOIs
Publication statusE-pub ahead of print - 29 Nov 2018

Fingerprint

Molecular imaging
Raman spectroscopy
Raman scattering
Nanoprobes
P-Selectin
Vascular Cell Adhesion Molecule-1
Biomarkers
Intercellular Adhesion Molecule-1
Imaging techniques
Antibodies
Endothelial cells
Medical imaging
Risk management
Gold
Risk assessment
Adhesion
Nanoparticles
Molecules

Keywords

  • atherosclerosis
  • molecular imaging
  • multiplexing
  • vascular inflammation
  • surface-enhanced Raman spectroscopy (SERS)

Cite this

Noonan, J., Asiala, S., Grassia, G., MacRitchie, N., Gracie, K., Carson, J., ... Maffia, P. (2018). In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. 8(22), 6195-6209. https://doi.org/10.7150/thno.28665
Noonan, Jonathan ; Asiala, Steven ; Grassia, Gianluca ; MacRitchie, Neil ; Gracie, Kirsten ; Carson, Jake ; Moores, Matthew ; Girolami, Mark ; Bradshaw, Angela ; Guzik, Thomas J. ; Meehan, Gavin R. ; Scales, Hannah ; Brewer, James M. ; McInnes, Iain B. ; Sattar, Naveed ; Faulds, Karen ; Garside, Paul ; Graham, Duncan ; Maffia, Pasquale. / In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. 2018 ; Vol. 8, No. 22. pp. 6195-6209.
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abstract = "Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis. The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi parameter molecular imaging technologies have been established to date. Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS).Methods: A series of antibody-functionalized gold nanoprobes (BFNP) were designed containing unique Raman signals in order to detect intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin using SERS.Results: SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin in vitro on human endothelial cells and ex vivo in human coronary arteries. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes.Conclusion: This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation in vivo and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.",
keywords = "atherosclerosis, molecular imaging, multiplexing, vascular inflammation, surface-enhanced Raman spectroscopy (SERS)",
author = "Jonathan Noonan and Steven Asiala and Gianluca Grassia and Neil MacRitchie and Kirsten Gracie and Jake Carson and Matthew Moores and Mark Girolami and Angela Bradshaw and Guzik, {Thomas J.} and Meehan, {Gavin R.} and Hannah Scales and Brewer, {James M.} and McInnes, {Iain B.} and Naveed Sattar and Karen Faulds and Paul Garside and Duncan Graham and Pasquale Maffia",
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Noonan, J, Asiala, S, Grassia, G, MacRitchie, N, Gracie, K, Carson, J, Moores, M, Girolami, M, Bradshaw, A, Guzik, TJ, Meehan, GR, Scales, H, Brewer, JM, McInnes, IB, Sattar, N, Faulds, K, Garside, P, Graham, D & Maffia, P 2018, 'In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy' vol. 8, no. 22, pp. 6195-6209. https://doi.org/10.7150/thno.28665

In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. / Noonan, Jonathan; Asiala, Steven; Grassia, Gianluca; MacRitchie, Neil; Gracie, Kirsten; Carson, Jake; Moores, Matthew; Girolami, Mark; Bradshaw, Angela; Guzik, Thomas J.; Meehan, Gavin R.; Scales, Hannah; Brewer, James M.; McInnes, Iain B.; Sattar, Naveed; Faulds, Karen; Garside, Paul; Graham, Duncan; Maffia, Pasquale.

Vol. 8, No. 22, 29.11.2018, p. 6195-6209.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy

AU - Noonan, Jonathan

AU - Asiala, Steven

AU - Grassia, Gianluca

AU - MacRitchie, Neil

AU - Gracie, Kirsten

AU - Carson, Jake

AU - Moores, Matthew

AU - Girolami, Mark

AU - Bradshaw, Angela

AU - Guzik, Thomas J.

AU - Meehan, Gavin R.

AU - Scales, Hannah

AU - Brewer, James M.

AU - McInnes, Iain B.

AU - Sattar, Naveed

AU - Faulds, Karen

AU - Garside, Paul

AU - Graham, Duncan

AU - Maffia, Pasquale

PY - 2018/11/29

Y1 - 2018/11/29

N2 - Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis. The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi parameter molecular imaging technologies have been established to date. Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS).Methods: A series of antibody-functionalized gold nanoprobes (BFNP) were designed containing unique Raman signals in order to detect intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin using SERS.Results: SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin in vitro on human endothelial cells and ex vivo in human coronary arteries. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes.Conclusion: This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation in vivo and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.

AB - Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis. The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi parameter molecular imaging technologies have been established to date. Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS).Methods: A series of antibody-functionalized gold nanoprobes (BFNP) were designed containing unique Raman signals in order to detect intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin using SERS.Results: SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin in vitro on human endothelial cells and ex vivo in human coronary arteries. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes.Conclusion: This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation in vivo and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.

KW - atherosclerosis

KW - molecular imaging

KW - multiplexing

KW - vascular inflammation

KW - surface-enhanced Raman spectroscopy (SERS)

UR - http://www.thno.org/

U2 - 10.7150/thno.28665

DO - 10.7150/thno.28665

M3 - Article

VL - 8

SP - 6195

EP - 6209

IS - 22

ER -

Noonan J, Asiala S, Grassia G, MacRitchie N, Gracie K, Carson J et al. In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. 2018 Nov 29;8(22):6195-6209. https://doi.org/10.7150/thno.28665