Rational design of a ratiometric fluorescent nanoprobe for real-time imaging of hydroxyl radical and its therapeutic evaluation of diabetes

Hydroxyl radical (center dot OH), one of the most reactive and deleterious substances in organisms, belongs to a class of reactive oxygen species (ROS), and it has been verified to play an essential role in numerous pathophysiological scenarios. However, due to its extremely high reactivity and short lifetime, the development of a reliable and robust method for tracking endogenous center dot OH remains an ongoing challenge. In this work, we presented the first ratiometric fluorescent nanoprobe NanoDCQ-3 for center dot OH sensing based on oxidative C-H abstraction of dihydroquinoline to quinoline. The study mainly focused on how to modulate the electronic effects to achieve an ideal ratiometric detection of center dot OH, as well as solving the inherent problem of hydrophilicity of the probe, so that it was more conducive to monitoring center dot OH in living organisms. The screened-out probe NanoDCQ-3 exhibited an exceptional ratiometric sensing capability, better biocompatibility, good cellular uptake, and appropriate in vivo retention, which has been reliably used for detecting exogenous center dot OH concentration fluctuation in living cells and zebrafish models. More importantly, NanoDCQ-3 facilitated visualization of center dot OH and evaluation of drug treatment efficacy in diabetic mice. These findings afforded a promising strategy for designing ratiometric fluorescent probes for center dot OH. NanoDCQ-3 emerged as a valuable tool for the detection of center dot OH in vivo and held potential for drug screening for inflammation-related diseases.