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

Abstract

Schistosomiasis remains a formidable global health threat, yet current diagnostic modalities like microscopy and ultrasonography suffer from limited sensitivity and critical inability for real-time in vivo monitoring, posing significant hurdles in precise infection staging. To address this diagnostic bottleneck, we develop a de novo strategic charge-regulation approach for developing a dual-channel near-infrared fluorescent probe toward hepatic γ-glutamyltranspeptidase (GGT), a key biomarker for schistosomiasis-induced liver pathological evolution. By engineering quinoline scaffold from zwitterionic, single positive charge, to double positive charge, the optimized probe QMC-N-GGT achieves superior precise targeting to the infected liver tissues with anionic microenvironment. Impressively, its dual-channel signals make a breakthrough to track when, where, and how the probe targets the liver and in situ lights up endogenous GGT. This probe exhibits a remarkable stage-dependent fluorescent response to GGT, enabling accurate distinction of slight, middle, 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.