Debut of a novel AIE-based fluorescent probe as tyrosinase tracer to image skin pigmentary disorders

Tyrosinase (TYR) functions as the critical enzyme in biosynthesis of melanin, and its abnormality is an important hallmark for skin pigmentary disorders. This renders the visualization of tyrosinase dynamics a strategically vital way to facilitate clinical diagnostic and monitoring. However, the use of small molecule fluorescent probes to assess tyrosinase levels and evaluate related therapeutics and drugs has been limited. This is mainly due to the aggregation-induced quenching (ACQ) effects of existing fluorescent probes. In this study, we introduce the first aggregation-induced emission (AIE) small molecule fluorescent probe, BTFTYR, for simple, highly sensitive, and effective detection of tyrosinase activity. The specific fluorescence signal generated by tyrosinase catalytic reaction enables the imaging of pigment cells. We demonstrate its application in visualizing tyrosinase with high contrast in living vertebrates, benefiting from the inherent photobleaching resistance of AIE materials, large Stokes shift, and considerable tissue permeability. We also show the outstanding skin penetration capability of BTFTYR in a skin model. Moreover, we present the first comprehensive evaluation of relevant clinical therapeutic approaches or drugs, including ultraviolet B (UVB) irradiation, kojic acid, and α-MSH, by interpreting the tyrosinase variation with BTFTYR. Finally, our studies confirm that BTFTYR neither causes skin inflammation nor produces visceral toxicity, making it a promising chemical tool for medical diagnosis and drug screening. This tool may further help elucidate the pathomechanisms associated with tyrosinase.