One-Pot Synthesis of Polysaccharide–Diphenylalanine Ensemble with Gold Nanoparticles and Dye for Highly Efficient Detection of Glutathione

Glutathione (GSH) plays a crucial role in various physiological processes. Therefore, efficient detection of GSH is of great importance. In this study, we present a new and highly efficient ratiometric fluorescent biosensor through one-pot synthesis of coupling the self-assembly of polysaccharide (alginate dialdehyde, ADA)-dipeptide (diphenylalanine, FF) and in situ reduction of gold nanoparticles (Au NPs) simultaneously encapsulating a dye (5-aminofluorescein, FI-NH₂) inside to form ADA-Au-FF-dye nanospheres. Because the fluorescence of the dye can be quenched by Au NPs and linearly recovered following the introduction of different GSH concentrations owing to nanometal surface energy transfer on and off, this new ADA-Au-FF-dye hybrid nanosphere-based sensor allows label-free and ratiometric detection of intracellular GSH and other biothiols in a wide linear range, which is of great significance for cancer diagnostics and therapy.