Charge-regulated hepatic γ-glutamyltranspeptidase fluorescent probe: in vivo staging of Schistosoma infection

Abstract

Schistosomiasis remains a formidable global health threat, yet with the limited sensitivity and critical inability of real-time in vivo monitoring using current diagnostic modalities such as microscopy and ultrasonography, there are significant hurdles to overcome before precise infection staging can be performed. To address this diagnostic bottleneck, we developed a de novo strategic charge-regulation approach with a dual-channel near-infrared fluorescent probe that binds to hepatic γ-glutamyltranspeptidase (GGT), a key biomarker for schistosomiasis-induced liver pathological evolution. By engineering quinoline scaffolding from zwitterionic, single-positive charge, to double-positive charge, the optimized probe QMC-N-GGT achieved superior precise targeting of infected liver tissues in an anionic microenvironment. Impressively, its breakthrough dual-channel signals enable tracking of when, where, and how the probe targets the liver and illuminates endogenous GGT in situ. This probe exhibits a remarkable stage-dependent fluorescent response to GGT, enabling accurate distinction of slight, moderate, and severe infection stages with an ultra-high signal-to-noise ratio. QMC-N-GGT thus represents an unprecedented diagnostic tool, bridging the gap between conventional infection screening and advanced pathological staging for non-invasive, real-time schistosomiasis monitoring.