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Activation mechanism of the nanoplatform AuNCs@MnO 2 nanosheets for GSH detection and intracellular imaging. [Display omitted] • A novel GSH-switched fluorescence nanoprobe has been constructed based on the integration between the inner filter effect of MnO 2 nanosheets and GSH-induced enhanced fluorescence of AuNCs. • The nanoplatform exhibits a high sensitivity for the detection of GSH with a low limit detection of 68 nM. • The nanoplatform achieves outstanding selectivity towards intracellular GSH over cysteine, homocysteine and ascorbic acid. • And that, it can selectively monitoring the GSH in human serum and the fluorescence imaging of endogenous GSH in living cell. Glutathione (GSH) plays a critical role in biological defense system and is associated with numerous human pathologies. However, it still remains a challenge for fluorescent detection of GSH over cysteine (Cys) and homocysteine (Hcy) because of their similar structures. In this work, MnO 2 nanosheets can efficiently quench the fluorescence of gold nanoclusters (Met-AuNCs) prepared by blending methionine and HAuCl 4 owing to their superior absorption capability. However, GSH can reduce MnO 2 nanosheets into Mn2+ which leads to the fluorescence recovery of Met-AuNCs. More intriguingly, GSH can dramatically and selectively enhance the fluorescence intensity of Met-AuNCs. Hence, a low background, ultrasensitive fluorescent detection of GSH was obtained with a detection limit of 68 nM. Moreover, the assay has been successfully used for GSH detection in human serum samples and cellular imaging with high selectivity over Cys and Hcy. [ABSTRACT FROM AUTHOR]