Pursuing shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) for concomitant detection of breast lesions and microcalcifications

Abstract

Although tissue staining followed by morphologic identification remains the gold standard for diagnosis of most cancers, such determinations relying solely on morphology are often hampered by inter- and intra-observer variability. Vibrational spectroscopic techniques, in contrast, offer objective markers for diagnoses and can afford disease detection prior to alterations in cellular and extracellular architecture by furnishing a rapid "omics"-like view of the biochemical status of the probed specimen. Here, we report a classification approach to concomitantly detect microcalcification status and local pathological state in breast tissue, featuring a combination of vibrational spectroscopy that focuses on the tumor and its microenvironment, and multivariate data analysis of spectral markers reflecting molecular expression. We employ the unprecedented sensitivity and exquisite molecular specificity offered by Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) to probe the presence of calcified deposits and distinguish between normal breast tissues, fibroadenoma, atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). By correlating the spectra with the corresponding histologic assessment, we developed partial least squares-discriminant analysis derived decision algorithm that provides excellent diagnostic power in the fresh frozen sections (overall accuracy of 99.4% and 93.6% using SHINs for breast lesions with and without microcalcifications, respectively). The performance of this decision algorithm is competitive with or supersedes that of analogous algorithms employing spontaneous Raman spectroscopy while enabling facile detection due to the considerably higher intensity of SHINERS. Our results pave the way for rapid tissue spectral pathology measurements using SHINERS that can offer a novel stain-free route to accurate and economical diagnoses without human interpretation.

The Clinical Application of Raman Spectroscopy for Breast Cancer Detection

“…Researchers have also utilized the Au@SiO2 SHINERS technique to detect NB tissues, fibroadenoma (FD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Compared with traditional Raman spectroscopy, SHINERS can provide more spectral feature information ( Figure 2) [24,25].…”

“…By correlating the spectra with the corresponding histologic assessment, the study developed partial least squares discriminant analysisderived decision algorithm that provides excellent diagnostic power in the fresh frozen sections (overall accuracy of 99.4% and 93.6% using SHINs for breast lesions with and without microcalcifications, resp.) [24,64].…”

“…Therefore, based on distinctive spectral features and intensity differences, we could discriminate normal, benign, and malignant. In recent years, many research papers have also shown the availability of Raman spectroscopy to classify diseased tissue in the breast [7,24] and especially for intraoperative margin assessment and SLNB for breast cancer. .…”

Silica‐Coated Plasmonic Metal Nanoparticles in Action

“…[46] Apart from reaction monitoring, SHINERS has been employed, for instance, in pesticide detection, as shown in Figure 8h-j, or for breast cancer type identification. [45,133] Mesoporous silica is however usually preferred, as it provides protection to the particles while allowing the diffusion of analytes toward the plasmonic surface. As shown in Figure 6, mesoporous silica coatings with radially oriented channels can be employed to template the growth of Au tips from encapsulated Au cores, achieving high colloidal stability in the absence of surfactants or polymeric ligands.…”

Cytochrome c‐Capped Fluorescent Gold Nanoclusters: Imaging of Live Cells and Delivery of Cytochrome c

“…In recent years, fluorescent noble-metaln anoclusters (NCs) have attracted speciala ttention because of their versatile applications. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Spatialc onfinement of free electrons in metal NCs resultsi nd iscrete and size-tunable electronic transitions, leadingt om olecular-like properties and bright luminescence. Hence, they are widely used as next-generation fluorophores for highly sensitive opticalimaging of live cells.…”