Self-Amplified Activatable Fluorescent Probe for Early Diagnosis of Acute Kidney Injury and High-Throughput Screening of Natural Protectants

Early diagnosis of acute kidney injury (AKI) and identification of effective therapeutics remain significant clinical challenges. Herein, we developed an activatable near-infrared fluorescent nanoprobe (denoted PS-QRC) by encapsulating a self-amplifying fluorescent sensor (QRCy) within kidney-targetable L-serine-functionalized ultrasmall poly(amidoamine) (PAMAM-Ser) dendrimers. Upon activation by reactive oxygen species (ROS), QRCy undergoes self-fragmentation, releasing four fluorophores to amplify the fluorescence signal, affording an ultra-low detection limit of 81 nM for hydrogen peroxide. The L-serine modification enables specific binding of PS-QRC to kidney injury molecule-1 (KIM-1), which is overexpressed in injured renal tubules, thereby promoting renal accumulation and reducing background interference. Impressively, PS-QRC allows noninvasive real-time imaging of cisplatin-induced AKI in mice as early as 12 h, significantly earlier than conventional serum biochemical and histopathological analyses. Furthermore, a high-throughput screening platform was established using this nanoprobe to evaluate natural products, from which chrysin was identified as a promising renoprotective agent. Chrysin demonstrated both in vitro and in vivo renoprotective effects, with efficacy comparable to the established antioxidant N-acetylcysteine. Moreover, PS-QRC enabled quantitative monitoring of chrysin's dose-dependent therapeutic response. Overall, this integrated probe provides a sensitive and reliable tool for early AKI diagnosis and the high-throughput discovery of novel renoprotective drugs.