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Theranostics 2018; 8(22):6195-6209. doi:10.7150/thno.28665 This issue Cite

Research Paper

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

Jonathan Noonan^1,*, Steven M. Asiala^2,*, Gianluca Grassia¹, Neil MacRitchie¹, Kirsten Gracie², Jake Carson³, Matthew Moores³, Mark Girolami^4,5, Angela C. Bradshaw⁶, Tomasz J. Guzik^6,7, Gavin R. Meehan¹, Hannah E. Scales¹, James M. Brewer¹, Iain B. McInnes¹, Naveed Sattar⁶, Karen Faulds², Paul Garside¹, Duncan Graham^2✉, Pasquale Maffia^1,6,8✉

1. Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
2. Centre for Molecular Nanometrology, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom;
3. Department of Statistics, University of Warwick, Coventry, United Kingdom;
4. Department of Mathematics, Imperial College London, London, United Kingdom;
5. The Alan Turing Institute, London, United Kingdom;
6. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
7. Department of Internal and Agricultural Medicine, Jagiellonian University College of Medicine, Kraków, Poland;
8. Department of Pharmacy, University of Naples Federico II, Naples, Italy.
*Drs. Noonan and Asiala are joint first authors.

✉ Corresponding author: Dr Pasquale Maffia, Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, Veterinary and Life Sciences, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK; Pasquale.Maffiaac.uk; and Prof Duncan Graham, Centre of Molecular Nanometrology, Department of Pure and Applied Chemistry, University of Strathclyde, Technology and Innovation Centre, 99 George Street, G1 1RD, UK; Duncan.grahamac.uk. More

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)

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