Screening of Methylglyoxal Fluctuations in the Kidneys of Diabetic Nephropathy Mice Using a Europium(III) Complex-Based Dual-Mode Luminescence Probe

The global surge in diabetes mellitus (DM) and its associated complications has prompted significant efforts to mitigate this growing public health challenge. Among these complications, diabetic nephropathy (DN) is of particular concern due to its high rates of morbidity and mortality. Extensive research has identified methylglyoxal (MGO) and MGO-derived advanced glycation end products (AGEs) as critical contributors to the pathogenesis of DN. Thus, there is a pressing need for precise and effective methodologies for monitoring MGO levels in complicated biological systems. Herein, we report the first Eu³⁺ complex-based dual-mode luminescence probe, <b>DAPTTA-Eu</b>^<b>3+</b>, for accurate MGO detection using time-gated luminescence (TGL) and luminescence lifetime measurements. The probe initially exists in a "dark state" characterized by a relatively short luminescence lifetime. Upon interaction with MGO, intense Eu³⁺ emission is restored, accompanied by a significant increase in luminescence lifetime. These features enable <b>DAPTTA-Eu</b>^<b>3+</b> to serve as a reliable luminescence probe for accurate MGO quantification, utilizing TGL and the luminescence lifetime as complementary detection strategies. Moreover, the cell membrane-permeable derivative of the probe, <b>AM-DAPTTA-Eu</b>^<b>3+</b>, was prepared and used for TGL imaging of both exogenous and endogenous MGO in live cells, which also allowed the MGO fluctuations in the kidneys of DN mice and the nephroprotective effects of metformin against DN to be assessed. Notably, by exploiting the differential expressions of renal MGO, the DN and cisplatin-induced acute kidney injury (AKI) were successfully distinguished. These results underscored the practicability of <b>AM-DAPTTA-Eu</b>^<b>3+</b> across varying kidney-related pathophysiological conditions, suggesting its high potential in clinical DN diagnosis.