Abstract
The biological investigation and detection of esophageal cancers could be facilitated with an endoscopic technology to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and investigation through the sensitive and multiplexed detection of cell-surface biomarkers. Here, we demonstrate that the topical application and endoscopic imaging of a multiplexed cocktail of receptor-targeted SERS NPs enables the rapid detection of tumors in an orthotopic rat model of esophageal cancer. Antibody-conjugated SERS NPs were topically applied on the lumenal surface of the rat esophagus to target EGFR and HER2, and a miniature spectral endoscope featuring rotational scanning and axial pull-back was employed to comprehensively image the NPs bound on the lumen of the esophagus. Ratiometric analyses of specific vs. nonspecific binding enabled the visualization of tumor locations and the quantification of biomarker expression in agreement with immunohistochemistry and flow cytometry validation data.
Highlights
Esophageal cancer causes approximately one-sixth of all cancer-related deaths worldwide [1, 2]
Ratiometric images show the concentration ratios of EGFR-NPs vs. isotype-NPs (Fig. 4(d)) and HER2-NPs vs. isotype-NPs (Fig. 4(e)). These results demonstrate that multiplexed ratiometric imaging of targeted vs. untargeted surface-enhanced Raman-scattering (SERS) NPs reveal the location of the receptor-positive tumors, and quantify the EGFR and HER2 expression levels in agreement with flow-cytometry results (right-side plots in Figs. 4(d) and 4(e))
We have demonstrated an endoscopic imaging strategy for detecting and/or investigating gastrointestinal cancers that is based on the visualization of the molecular phenotype of tissues through the administration of molecularly targeted SERS NP contrast agents
Summary
Esophageal cancer causes approximately one-sixth of all cancer-related deaths worldwide [1, 2]. Over the past few decades, various types of exogenous contrast agents have been developed for the molecular imaging of fresh tissues ex vivo and in vivo [9,10,11] Among these contrast agents, surface-enhanced Raman-scattering (SERS) nanoparticles (NPs) have attracted interest for cancer imaging due to their excellent multiplexing capabilities [12]. The SERS NPs utilized in this study may be engineered as various “flavors,” each of which generates a unique Raman spectral “fingerprint” when illuminated with a single laser at 785 nm These diverse “barcode” or “fingerprint” spectra allow for the multiplexed detection of large panels of NPs when applied in live animals and human tissues [13,14,15,16,17,18]. Major challenges such as FDA approval and the improvement of imaging speeds must be addressed in order to translate this technique into clinical use
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