Imaging of ONOO− fluctuations during drug-induced liver/kidney injury in vitro and in vivo via a dicyanoisophorone-based NIR fluorescent probe with a large Stokes shift

Abstract

Current clinical indicators for assessing liver/kidney injury are functional rather than injury indicators, which may cause some delays in the diagnosis of drug-induced liver injury (DILI) and kidney injury (DIKI). Therefore, the development of noninvasive and real-time methods for the effective diagnosis of DILI/DIKI is of great benefit to their clinical management. Herein, we constructed a dicyanoisophorone-based near-infrared (NIR) fluorescent probe (PNDP). Upon the addition of ONOO⁻, the probe exhibits 111.4-fold fluorescence enhancement at 665 nm with a large Stokes shift of 175 nm as well as excellent selectivity, strong anti-interference capability, and a low limit of detection (118.9 nmol L⁻¹). More significantly, the PNDP was successfully employed for the sensitive detection of ONOO⁻ in living cells and DILI/DIKI mice models. In vitro and in vivo bioimaging experiments demonstrated that the PNDP has greater versatility and promising potential for use as a diagnostic agent for the diagnosis of drug-induced hepatotoxicity and nephrotoxicity by monitoring ONOO⁻ fluctuations.