Investigating the efficacy of a photoacoustic probe in liver function assessment for diabetic mellitus

γ -Glutamyltransferase (GGT, EC number: 2.3.2.2) is an enzyme critical for glutathione metabolism and serves as a key biomarker for liver function and disease. Diabetes mellitus, a prevalent metabolic disorder, often complicates liver function and increases the challenge of accurately monitoring hepatic GGT levels due to fluctuating metabolic conditions. In this study, we introduce a sulfonate-modified hemicyanine dye-based probe, HDP-GGT, designed for the targeted and real-time assessment of GGT activity in the liver. HDP-GGT combines the fluorescence and photoacoustic advantages of hemicyanine dyes with a specific peptide sequence that enhances sensitivity and specificity for GGT detection. Utilizing both in vitro and in vivo methodologies, the sulfonate-modified HDP-GGT probe enables dual-modal imaging of hepatic and serum GGT activity by photoacoustic and fluorescence models, respectively. To evaluate the clinical translational potential of HDP-GGT, we applied it to detect GGT in mouse serum, finding that the fluorescence signal intensity was highest in the diabetes mellitus (DM) group and significantly reduced in the diabetes mellitus + metformin (DM + Met) group, suggesting that HDP-GGT has promising clinical application prospects. Our results indicate that HDP-GGT is a potent tool for non-invasive monitoring of liver health and could play a crucial role in diagnosing and managing liver-related disorders, particularly in the context of diabetes.