The development of molecular probes for the detection and imaging of biological thiols is a major step forward diagnosing various types of diseases. Previously reported thiol imaging strategies were mainly based on a single mode of imaging with a limited application in vivo. In this work, we introduced an unsymmetrical near-infrared (NIR) squaraine dye (USq) as an exogenous contrast agent for photoacoustic and fluorescence bimodal imaging of thiol variations in live animals. USq exhibits a narrow absorption band at 680 nm that generates a photoacoustic signal and a strong NIR emission at 700 nm (ΦF = 0.27), which is applicable for deep tissue optical imaging. Both photoacoustic and fluorescence signals could selectively disappear in the presence of different thiols. Through in vitro and in vivo imaging studies, unique imaging capability of USq was demonstrated, and the effect of food uptake on the increased level of aminothiols in blood was confirmed.
