Plasmonic star-shaped gold nanoparticles for high-sensitive SERS-based detection of hepatocellular carcinoma (HCC).

Surface-enhanced Raman spectroscopy (SERS) has emerged as a promising analytical tool for sensitive molecular detection in biomedical applications. In this study, star-shaped gold nanoparticles (AuNSTs) were employed as plasmonic substrates to enhance Raman signals for the analysis of hepatocellular carcinoma (HCC) directly from whole blood samples. The synthesized AuNSTs exhibited strong plasmonic resonance, enabling significant electromagnetic field localization and signal amplification. A reproducible Raman feature at ∼700 cm-1 was consistently observed in HCC samples following nanoparticle integration, while it was not detected in healthy controls under the same experimental conditions. Although the precise biochemical origin of this feature remains to be fully elucidated, it is likely associated with alterations in biomolecular composition and nanoparticle-biomolecule interactions at plasmonic hotspots. Exosomal isolation further improved spectral clarity; however, AuNST-assisted measurements on whole blood provided sufficient spectral differentiation without the need for complex preprocessing. Chemometric analysis using principal component analysis (PCA) demonstrated clear separation between healthy and HCC samples, supporting the potential of this approach for spectral discrimination. Overall, this study presents a rapid, minimally invasive, and label-free SERS-based platform for the detection of HCC-associated spectral features in whole blood, with potential applications in clinical diagnostics and biosensing. Further studies are required to validate specificity and elucidate the molecular origin of the observed Raman signals.