Minimally invasive monitoring of acute liver injury using ROS-responsive gold aggregates for urinary readout

Acute liver injury is a life-threatening disorder associated with substantial morbidity and mortality worldwide, underscoring the need for convenient and minimally invasive monitoring. Here, we develop an ALI-responsive nanoprobe that dissociates into renal-clearable gold nanoparticles, facilitating minimally invasive acute liver injury diagnosis through colorimetric urinalysis. This nanoprobe is constructed as a simple nanoaggregate of self-assembled ultrasmall AuNPs linked via a responsive moiety (2,2'-[propane-2,2-diylbis(thio)]diacetic acid). Elevated endogenous reactive oxygen species in the injured liver trigger the dissociation of Au-TKs accumulated in hepatic tissue. The released AuNPs are subsequently excreted into urine and can be quantified by leveraging their peroxidase-like activity and renal-clearable property. This platform outperforms conventional serum-based methods in terms of sensitivity and accuracy for early prediction of acetaminophen-induced liver injury in mice. To enhance practicality, a smartphone application with color capture capability was developed, demonstrating excellent linearity (R² > 0.95) compared with microplate reader detection. This smartphone-based colorimetric biosensing system, featuring convenient, minimally invasive operation, holds strong potential to transform ALI monitoring through urinary readouts and may provide additional benefits for rapid detection of a broad range of inflammatory diseases by targeting disease-specific pathological signatures.