Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI. Given the revelation of myeloperoxidase overexpression and redox imbalance of ClO-/GSH in acute kidney injury (AKI), a tailored photoacoustic (PA) probe is developed that enables real-time, noninvasive monitoring of AKI levels through PA imaging. Leveraging this probe, this work has established a drug screening approach and has discovered, for the first time, the therapeutic potential of astragalin in treating AKI. image