We previously demonstrated SERS-BFNP imaging of intercellular adhesion molecule (ICAM)-1 in the microvasculature of a murine ear 20 however, whilst it has been shown that multiple BFNPs can be detected in tissues following local or non-targeted administration, targeted multiplex SERS imaging following intravenous injection has yet to be demonstrated 21, 22. SERS-active NPs have been successfully engineered to bind to biological molecules, with biofunctional nanoprobes (BFNP) composed of a NP core, reporter molecule, encapsulation layer and targeting biomolecule, facilitating the detection and discrimination of targeted biomarkers 16 - 19.
The spectral diversity of these reporter molecules and amenable NP surface chemistry make SERS highly attractive for multi-parameter molecular imaging 16, 17. SERS relies on noble metal nanoparticles (NPs) to enhance unique, fingerprint-like Raman signals from reporter molecules at or near the NP surface 15.
Surface-enhanced Raman spectroscopy (SERS) is a novel imaging modality with the potential to directly address these unmet clinical needs. In this respect, the inability to image vascular inflammation in patients at the molecular level and identify those with prominent inflammatory disease components has been identified as a key clinical limitation, as this may facilitate cardiovascular risk assessment and management 11, 12 - 14. Whilst inflammation plays a significant role in atherosclerosis onset and development, as well as plaque vulnerability, this understanding has not yet been successfully translated to allow for disease stratification or the reporting of successful intervention 9 - 11.
Diagnostic imaging technologies such as magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US) and positron emission tomography (PET) have facilitated the anatomic imaging of atherosclerosis however, these approaches lack the ability to predictively discriminate stable and vulnerable atherosclerotic disease 4 - 8. It underlies the majority of adverse cardiovascular disease (CVD) outcomes that are the leading cause of death worldwide 3. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes.Ĭonclusion: 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.Ītherosclerosis arises from a combination of interacting genetic and lifestyle factors, leading to metabolic dysfunction and chronic inflammation 1, 2. 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.
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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. Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS). 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.
Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis.
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