Cysteine-Triggered Hydrogen Sulfide Nanoprodrug for Real-Time Imaging and Therapeutic Evaluation of Acute Kidney Injury

Acute kidney injury (AKI) is associated with dysregulated cysteine (Cys) levels and oxidative stress. Hydrogen sulfide (H2S) plays a regulatory role in renal diseases with antioxidant and anti-inflammatory effects. However, tools for real-time monitoring of gas release and therapeutic response remain limited. Herein, we report a cysteine-triggered near-infrared (NIR) fluorescent H2S donor platform NIR-NRS (R = Me/Ph/H) based on hemicyanine fluorophores and a thiocarbamate moiety. Notably, NIR-NHS enables efficient H2S release accompanied by significant fluorescence enhancement (10-fold), allowing real-time visualization of gas generation. To improve biocompatibility and renal targeting, NIR-NHS was conjugated with bovine serum albumin (BSA) to construct nanoprodrugs (NIR-NHS@BSA10 and NIR-NHS@BSA100). Among them, NIR-NHS@BSA100 exhibits size-dependent H2S release behavior, efficient reactive oxygen species (ROS) scavenging, and oxidative stress recovery. In vivo studies demonstrate that NIR-NHS@BSA100 achieves efficient kidney targeting and allows real-time visualization of H2S release in response to elevated Cys levels. In cisplatin-induced AKI models, this system enables imaging-guided evaluation of therapeutic efficacy, reducing inflammatory cytokines (TNF-α and IL-1β). This work establishes an NIR imaging-based analytical platform for real-time monitoring and evaluation of H2S-based therapeutics in kidney injury.