A fluorescent/photoacoustic probe for imaging of hydroxyl radical and high-throughput screening of natural products to attenuate acute kidney injury

Abstract

Abstract The hydroxyl radical (•OH) has been shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH detection tool holds great promise for the early diagnosis of AKI and high-throughput screening (HTS) of inhibitors to attenuate AKI. In this work, we report the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI. CDIA has near-infrared (NIR) fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 hours using this probe is superior to the 48-hour detection time for typical clinical assays, such as blood urea nitrogen (BUN) and serum creatinine (sCr) detection. Furthermore, a method has been established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin has been screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual-mode tool for illuminating the •OH-related pathological process in AKI and for screening additional compounds to prevent and treat AKI.