In vivo 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 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.

Developing a xenograft model of human vasculature in the mouse ear pinna

“…This would allow us to visualise various aspects of immune cell behaviours, including extravasation, in real time using acute models of inflammation. Other applications in which a model of human vasculature would also be useful include diagnostic imaging in cardiovascular research 45 and drug screening in cancer studies 12 .…”

Prospects for Raman spectroscopy in cardiology

“…Кроме попыток неспецифической оценки состояния сосудистой стенки методом КР-спектроскопии, разрабатываются подходы, направленные на оценку отдельных молекул. Васкулярная молекула клеточной адгезии 1 -vascular cell adhesion molecule 1 (VCAM-1) представляет собой белок, входящий в суперсемейство иммуноглобулинов, участвующий в адгезии лейкоцитов и эндотелиальных клеток [33]. Предполагается, что обнаружение VCAM-1 может быть использовано для ранней диагностики атеросклероза [33].…”

“…Васкулярная молекула клеточной адгезии 1 -vascular cell adhesion molecule 1 (VCAM-1) представляет собой белок, входящий в суперсемейство иммуноглобулинов, участвующий в адгезии лейкоцитов и эндотелиальных клеток [33]. Предполагается, что обнаружение VCAM-1 может быть использовано для ранней диагностики атеросклероза [33]. Для исследования VCAM-1 в работе [34] (2014) предложили использовать метод КР-спектроскопии [34].…”

Optical Multiplexed Bioassays for Improved Biomedical Diagnostics

“…In comparison to fluorescence‐based techniques, Raman spectroscopy offers picomolar sensitivity with ultralow autofluorescence and high multiplexing capabilities. Although as a newly developed and non‐invasive preclinical imaging method, SERS has already shown good results in multiplexed vascular inflammation imaging, multiplexed imaging of tumor biomarkers, and multiplexed lymph‐node imaging . For example, five SERS nanoparticle types with unique fingerprint patterns were fabricated and used to carry out in vivo multiplexed imaging in the liver of living mice after intravenous injection.…”