Peroxynitrite-responsive dicyanoisophorone-xanthene NIR fluorescent probe for monitoring and therapeutic evaluation of diabetic liver injury

Chronic hyperglycemia in diabetes induced liver injury (DLI) may progress to irreversible outcomes without timely intervention. It is highly beneficial to the development of a simple and rapid method for the early and accurate diagnosis of DLI. In this study, we developed an activatable near-infrared (NIR) fluorescent probe (DCIP-ONOO) based on a dicyanoisophorone-xanthene scaffold, for monitoring and therapeutic evaluation of DLI via Peroxynitrite (ONOO⁻) imaging. Upon the addition of ONOO⁻, DCIP-ONOO exhibited a 27.6-fold fluorescence enhancement at 770 nm with an excellent selectivity, fast responsiveness, and a low limit of detection (119.6 nmol/L). In vitro imaging experiments confirmed that it was capable of being employed for the sensitive detection of ONOO⁻. More significantly, in a diabetic mice model, DCIP-ONOO was successfully used to achieve in vivo imaging of DLI and to monitor metformin-mediated symptom alleviation without causing any organ damages. These results established DCIP-ONOO as a potential tool for effective tracking of ONOO⁻ during diabetic hepatotoxicity.