An H2O2 and MPO programmable responsive MRI probe for early detection of drug-induced acute kidney injury via spatiotemporal monitoring of renal oxidative stress and inflammation

The sequential monitoring of two pathological processes has clinical significance for early detection of drug-induced acute kidney injury (AKI), but remains challenging due to the lack of spatiotemporal probes. Here, we developed a hydrogen peroxide (H 2 O 2 ) and myeloperoxidase (MPO) programmable responsive magnetic resonance imaging (MRI) probe (PAH-Gd) for spatiotemporal monitoring of renal oxidative stress and inflammation. Upon exposure to H 2 O 2 , PAH-Gd transformed into a kidney-targeting moiety, H–Gd, which selectively accumulated in kidneys and moderately enhanced renal T1-weighted imaging (T1 WI) signal. Subsequently, the H–Gd could be oxidized by MPO to form dimers or adducts with nearby proteins, further enhancing renal T1 WI signal. We found that PAH-Gd could perform spatiotemporal monitoring of renal oxidative stress and inflammation at 12 h and 24 h post-Cisplatin (DDP) administration, enabling early detection of DDP-induced AKI at least 60 h earlier than that of standard clinical assays and permitting dynamic monitoring of renal injury progression. The spatiotemporal T1 WI overcame the limitations in detecting diverse pathological processes with a single MRI probe, accurately reporting the drug-induced AKI in the early stage and contributing to AKI prevention and treatment in the clinic.