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

利用表面增强拉曼光谱技术对血管炎症进行体内多重分子成像

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

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.

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