Quantitative molecular phenotyping with topically applied SERS nanoparticles for intraoperative guidance of breast cancer lumpectomy

Abstract

There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases 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. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15 minutes for potential intraoperative use in guiding breast-conserving surgeries.

Cancer characterization and diagnosis with SERS-encoded particles

“…For example, Wang et al (2016) have demonstrated the possibility of direct staining and imaging of mouse HER-2 positive breast tumor tissues by applying SEPs functionalized with anti-HER2, followed by a rapid rinse with serum to remove unspecifically deposited SEPs (Fig. 5).…”

Evaluation of breast tissue with confocal strip-mosaicking microscopy: a test approach emulating pathology-like examination

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Confocal microscopy is an emerging technology for rapid imaging of freshly excised tissue without the need for frozen-or fixed-section processing. Initial studies have described the major findings of invasive breast cancers using fluorescence confocal microscopy.…”

Optical coherence elastography – OCT at work in tissue biomechanics [Invited]

“…Adding mechanical contrast to the scattering contrast shows the promise of resolving this issue, whilst employing conventional OCT resolution. Finally, on the topic of breast cancer, other groups have examined breast tissues using a variety of methods [159]: strain-based [160] and dynamic OCE [41], high-resolution OCT and its variants [161,162], in vivo probe-based OCT in the excision cavity [163], photoacoustic tomography methods [164] and Raman spectroscopy of nanoparticle contrast agents [165]. It is not yet clear which method will prove best, but beyond accurate assessment of involved tissue, the application to margin assessment will require ready assessment by the surgeon of all relevant tissue in less than 30 min in total, and will likely favor an intra-cavity solution [163].…”