Thiol–Disulfide Exchange Reaction for Cellular Glutathione Detection with Surface-Enhanced Raman Scattering

Abnormal glutathione (GSH) levels are related to several diseases, including cancer. In this paper, surface-enhanced Raman spectroscopy (SERS) based on a 2-(pyridyldithio)ethylamine (PDEA)-modified AgNPs@Si wafer is proposed for intracellular GSH detection. PDEA plays multifunctional roles in the method, including the participation in the thiol–disulfide exchange reaction and the contribution of a great SERS signal reporter. With the addition of GSH, the disulfide bond of PDEA will be broken, releasing the pyridine ring in PDEA and resulting in a signal-off SERS response. The developed specific reaction-based SERS assay can detect GSH levels as low as 2.5 × 10–7 M. Subsequently, we employed this method to evaluate cellular GSH levels and found that the levels in cancer cells are higher than those in normal cells. The PDEA-modified AgNPs@Si-based SERS protocol demonstrates good selectivity and high sensitivity, as well as robustness, which is suitable to evaluate cellular GSH levels.