Surgical Guidance via Multiplexed Molecular Imaging of Fresh Tissues Labeled With SERS-Coded Nanoparticles

Abstract

The imaging of dysregulated cell-surface receptors (or biomarkers) is a potential means of identifying the presence of cancer with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Recently, surface-enhanced Raman-scattering (SERS) nanoparticles (NPs) have attracted wide interest due to their potential for sensitive and multiplexed biomarker detection. In this review, we focus on the most recent advances in tumor imaging using SERS-coded NPs. A brief introduction of the structure and optical properties of SERS NPs is provided, followed by a detailed discussion of key imaging issues such as the administration of NPs in tissue (topical versus systemic), the optical configuration and imaging approach of Raman imaging systems, spectral demultiplexing methods for quantifying NP concentrations, and the disambiguation of specific vs. nonspecific sources of contrast through ratiometric imaging of targeted and untargeted (control) NP pairs. Finally, future challenges and directions are briefly outlined.

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection‐Enhanced Topical Staining with SERS‐Coded Nanoparticles

“…[10,15a,16] While these results were valuable for demonstrating the feasibility of the REMI approach for identifying residual tumors at the surfaces of fresh excised tissues, improving the degree of multiplexing would further improve the sensitivity of REMI for tumor detection. Previous studies have used untargeted SERS NPs to show that the multiplexed imaging of up to ten flavors of SERS NP is feasible.…”

Multimodal assessment of SERS nanoparticle biodistribution post ingestion reveals new potential for clinical translation of Raman imaging

“…One of the biggest challenges faced by oncologic surgeons in the operating room is determining where the tumor they are resecting begins and ends. These tumor targeting SERS nanoparticles could be applied topically to the oral cavity in the form of a rinse and, when used with a handheld Raman imaging device [16, 17, 19, 22, 24], provide surgeons with a molecular imaging map that offers objective, actionable information in real-time to guide tumor resection and thereby improve patient outcomes.…”

Spatial Analysis of Metal–PLGA Hybrid Microstructures Using 3D SERS Imaging

“…[3] One example is given by surface-enhanced Raman scattering (SERS), a ultrasensitive imaging tool, which, in combination with engineered particle systems, has already found a variety of applications. [4,5] The ability to tune the excitation wavelength into the near infrared (NIR) range, the so-called biological transparency window (650-950 nm), leads to improved light penetration in living tissue, while the low Raman cross section of water and the potential for multiplexed measurements over long periods of time, render this technique ideal for nanomedicine applications. [5][6][7] For example, Contag, Gambhir, and co-workers recently introduced a Raman spectrometer coupled to an endoscope for SERS-based endoscopy.…”

“…[4,5] The ability to tune the excitation wavelength into the near infrared (NIR) range, the so-called biological transparency window (650-950 nm), leads to improved light penetration in living tissue, while the low Raman cross section of water and the potential for multiplexed measurements over long periods of time, render this technique ideal for nanomedicine applications. [5][6][7] For example, Contag, Gambhir, and co-workers recently introduced a Raman spectrometer coupled to an endoscope for SERS-based endoscopy. [8,9] Crucial for this and other applications are nanoparticles functionalized with Raman active molecules (SERS-tags).…”

“…[8,9] Crucial for this and other applications are nanoparticles functionalized with Raman active molecules (SERS-tags). [5,10] A common strategy toward achieving stable, SERS active nanostructured materials, comprises the integration of both polymers and gold nanoparticles into hybrid materials. Recent examples have been reported for a variety of systems, where, e.g., a thin polymer shell acts as the particle stabilizer, the polymer itself being used as the SERS tag, or where gold particles are embedded in SERS tag-loaded hydrogels.…”