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

Research Paper

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

Jonathan Noonan1,*, Steven M. Asiala2,*, Gianluca Grassia1, Neil MacRitchie1, Kirsten Gracie2, Jake Carson3, Matthew Moores3, Mark Girolami4,5, Angela C. Bradshaw6, Tomasz J. Guzik6,7, Gavin R. Meehan1, Hannah E. Scales1, James M. Brewer1, Iain B. McInnes1, Naveed Sattar6, Karen Faulds2, Paul Garside1, Duncan Graham2✉, Pasquale Maffia1,6,8✉

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.

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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How to cite this article:
Noonan J, Asiala SM, Grassia G, MacRitchie N, Gracie K, Carson J, Moores M, Girolami M, Bradshaw AC, Guzik TJ, Meehan GR, Scales HE, Brewer JM, McInnes IB, Sattar N, Faulds K, Garside P, Graham D, Maffia P. In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. Theranostics 2018; 8(22):6195-6209. doi:10.7150/thno.28665. Available from http://www.thno.org/v08p6195.htm