An inherently kidney-targeting near-infrared fluorophore based probe for early detection of acute kidney injury

Acute kidney injury (AKI) is common in hospital patients. Delayed diagnosis and treatment of AKI due to the lack of efficient early diagnosis is an important cause of its high mortality. While fluorescence imaging seems promising to non-intrusively interrogate AKI-related biomarkers, the low kidney contrast of many fluorophores conferred by their relatively low abundance of distribution in the kidney limits their application for AKI detection. Herein, we discovered a near-infrared fluorophore with inherent kidney-targeting ability. Based on this fluorophore, a fluorogenic probe (KNP-1) was developed by targeting peroxynitrite (ONOO−), which is upregulated at the early onset of AKI. KNP-1 exhibits desirable kidney distribution after intravenous administration and is fluorescent only after activation by ONOO−. These properties lead to excellent kidney contrast imaging results. KNP-1 is capable of detecting both nephrotoxin-induced and ischemia-reperfusion injury-induced AKI in live mice. Temporally resolved imaging of AKI-disease model mice with KNP-1 suggests a gradual increase in renal ONOO− levels with disease progression. Notably, the upregulation of ONOO− can be observed at least 24 h earlier than the clinically popular sCr and BUN methods. Blocking ONOO− generation also proves beneficial. These results highlight the applicability of this inherently tissue targeting-based strategy for designing probes with desirable imaging contrast; potentiate ONOO− as a biomarker and target for AKI early diagnosis and medical intervention; and imply the clinical relevance of KNP-1 for AKI early detection.