A Self-Alarming Nanoantidote for Early Urinary Diagnosis and Antioxidative Therapy of Drug-Induced Acute Kidney Injury

Timely detection and intervention of drug-induced acute kidney injury (AKI) during pharmacotherapy are critical to prevent renal damage and extend the therapeutic window of nephrotoxic drugs. Herein, we report a self-alarming fluorescence-enhanced nanoantidote (SAFEN) formed by the self-assembly of boronic acid-modified fluorescein with caged fluorescence, antioxidative tannic acid (TA), and polyethylene glycol (PEG). SAFEN is designed to delay AKI onset during the administration of nephrotoxic medications owing to antioxidative effects of TA. More importantly, once nephrotoxicity exceeds the protective ability of SAFEN, the caged fluorescence can be specifically activated by pathological reactive oxygen species (ROS), a prodromal biomarker of AKI, enabling real-time alarming of AKI via urinary fluorescence analysis and suggesting timely adjustment of the treatment regimen. In this way, SAFEN realizes a much earlier diagnosis of AKI than existing clinical methods. The theranostic effectiveness of SAFEN is verified in multiple murine and preclinical porcine AKI models, demonstrating great clinical promise for nephrotoxin management.