<i>In vivo</i> multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy

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 <i>in vivo</i> imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS). <b>Methods:</b> 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. <b>Results:</b> SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin <i>in vitro</i> on human endothelial cells and <i>ex vivo</i> in human coronary arteries. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated <i>in vivo</i> following intravenous injection of the nanoprobes. <b>Conclusion:</b> This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation <i>in vivo</i> and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.