Biothiols,such as cysteine (Cys) and homocysteine (Hcy),play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems.Therefore,the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression.In this work,we developed a near-infrared (NIR) fluorescence and photoacoustic dual-modal molecular probe (NIR-S) that can be specifically activated by Cys or Hcy.The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction,resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys.Thus,NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution,but also can be applied to living cells and mice to detect Hcy/Cys.This work provided a practical tool to detect Hcy/Cys levels in vivo,which would be beneficial for the early diagnosis and progress of diseases.