A copper-mediated on–off–on gold nanocluster for endogenous GSH sensing to drive cancer cell recognition

The sensitive and selective detection of endogenous glutathione (GSH) is of great significance due to its key role in physiological and pathological processes. Herein, we report a novel on–off–on transferrin (Tf)-coated gold nanocluster (AuNCs@Tf) with low toxicity, good stability and intense red fluorescence which can enter living cells and is mainly located in lysosomes. In addition, the fluorescence of AuNCs@Tf is quenched by Cu²⁺, indicating its sensitivity to Cu²⁺ with a detection limit of 0.23 μM at pH 4.5. Interestingly, we found that the quenched AuNCs@Tf–Cu²⁺ system only has a special affinity for GSH with a detection limit of 2.86 μM so that invisible AuNCs@Tf–Cu²⁺ can be gradually illuminated by endogenous GSH in the lysosomal environment of tumor cells with increase in time. More excitingly, the AuNCs@Tf–Cu²⁺ system can illuminate tumor cells rather than normal cells, resulting in its successful application in cancer cell recognition, which implies its great potential application in cancer diagnosis. Moreover, the AuNCs@Tf was also applied in Cu²⁺ strips and encryption/decryption of information.