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

Noonan, Jonathan and Asiala, Steven and Grassia, Gianluca and MacRitchie, Neil and Gracie, Kirsten and Carson, Jake and Moores, Matthew and Girolami, Mark and Bradshaw, Angela and Guzik, Thomas J. and Meehan, Gavin R. and Scales, Hannah and Brewer, James M. and McInnes, Iain B. and Sattar, Naveed and Faulds, Karen and Garside, Paul and Graham, Duncan and Maffia, Pasquale (2018) In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. Theranostics, 8 (22). pp. 6195-6209. ISSN 1838-7640

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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.