Electrochemical detection of intracellular glutathione based on ligand exchange assisted release of DNA-templated silver nanoparticles

•DNA sequences can be the template for AgNPs synthesis.•High-affinity binding of GSH and AgNPs can mediate ligand exchange reaction.•Dissolved AgNPs can arouse the ultra-sensitive electrochemical responses.•The method can specially monitor GSH in the serum samples and even Hela cells. Glutathione (GSH), the most abundant intracellular non-protein thiol species, plays vitally important roles in various physiological and pathological processes. In this work, we have proposed an effective electrochemical method for the detection of intracellular GSH based on the high-affinity binding of GSH and silver nanoparticles (AgNPs). AgNPs can be formed through the reduction of silver ions on the surface of a DNA template, and can be released from the template DNA through the ultra-stable Ag-S interaction in the presence of GSH. After removing the unreleased AgNPs from the reaction solution with the aid of the magnetic graphene, GSH-coated AgNPs can be dissolved to release a large amount of silver ions and thus lead to an obvious electrochemical response. The electrochemical results have shown that our method can sensitively and specially detect GSH in a wide linear range from 0.1nM to 1μM with a low detection limit of 2.3×10−11M, which can be successfully applied to detect the intracellular GSH extracted from Hela cells. Therefore, our method may have a great potential in the clinical diagnosis of the related diseases in the future.