Ratiometric Fluorescent Probe for Monitoring Endogenous Methylglyoxal in Living Cells and Diabetic Blood Samples

Optical imaging provides noninvasive powerful tools not only for better understanding the physiological and pathological roles of methylglyoxal (MGO) in living systems but also for potential clinical diagnosis of MGO-related diseases, such as diabetic complications. However, so far only very few turn-on MGO fluorescent sensors have been developed, and they are all based on the reaction between MGO and benzenediamines. Due to the possible reactions of benzenediamines with other cellular molecules, such as NO and FA, these sensors suffer from limited selectivity and potential deactivation in cells. Herein, we report a novel MGO recognition reaction using 2-aminoacetamide. The reaction between MGO and 2-aminoacetamide was found to be highly efficient and specific, with no interference from NO and FA in particular. This reaction was used to develop the first ratiometric fluorescent probe (CMFP) for MGO. We have proven that CMFP could detect MGO at physiological concentrations in both aqueous buffer and living cells with excellent selectivity and sensitivity. Furthermore, we successfully utilized CMFP to study intracellular MGO generation routes and evaluated MGO levels of clinic blood samples from healthy and diabetic patients. These results highlight the potential utility of this probe in both basic science research and clinical diagnosis.