Surface-enhanced confocal Raman microscopy to characterize esophageal cancer cell-derived extracellular vesicles and maternal cells

Exosomes, a subtype of extracellular vesicles, are increasingly recognized as promising biomarkers for human cancers. Rapid detection and classification of esophageal cancer-associated exosomes could significantly improve non-invasive screening for potential patients. This study aims to establish a label-free, direct surface-enhanced Raman scattering (SERS) method to capture characteristic molecular information from both esophageal cancer cells and their corresponding exosomes using confocal Raman microscopy. The results revealed distinct Raman spectra for esophageal cancer cells and their exosomes within the range of 500-1600 cm^-1, with notable signal similarities observed at 506-622, 778-832, 1079-1098, and 1572-1630 cm^-1. In contrast, significant differences were identified in Raman peaks related to nucleic acids (723, 654, 1354 cm^-1) and proteins (998, 1028, 1354, 1560 cm^-1). An orthogonal partial least squares discriminant analysis (OPLS-DA) model was utilized to discern subtle variations among these highly similar samples, achieving an accuracy rate of 100%. By comparing the spectral correlations between esophageal cancer cells and their exosomes, this study provides valuable insights into the molecular composition and cellular origins of exosomes. The findings demonstrate the potential of integrating SERS with OPLS-DA for the precise and rapid detection and monitoring of esophageal cancer through exosomal biomarkers, offering a powerful tool for diagnostic applications.