As vital important bioactive species, human serum albumin (HSA) and sulfur dioxide (SO 2 ) are essential molecules in the organisms and act a pivotal part in many biological events. Although studies have shown that SO 2 -induced HSA radicals can cause oxidative damage, the underlying mechanism of the synergistic effect of HSA and SO 2 in various diseases is obscure, mainly because of the lack of powerful tools that can simultaneously detect HSA and SO 2 in living systems. In this work, we report a novel single-site, double-sensing fluorescent probe 1 for the simultaneous detection of HSA and SO 2 . The probe is based on our finding that HSA can catalyze a Michael addition reaction between the probe and SO 2 , which induces a change in fluorescence. Probe 1 can effectively entered the endoplasmic reticulum and can be used to image exogenously introduced and de novo synthesis of HSA in endoplasmic reticulum. Furthermore, the simultaneous detection of HSA and SO 2 was realized for the first time with probe 1. More important, we observed that HSA still retains its activity to catalyze the Michael addition reaction of 1 and SO 2 in living cells, which may provide a significant boost in the study of the role of HSA in medicine and pharmacy.

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