Esterase fluorescent probe for precise diagnosis of diabetes and dynamic monitoring of insulin therapy.

BACKGROUND

A hallmark of diabetes is persistent hyperglycemia, a condition highly prone to inducing oxidative stress and triggering multi-organ damage. As the central hub for glucose and lipid metabolism, the liver is particularly vulnerable to such injury. Alterations in esterase activity are closely associated with the metabolic disturbances observed in diabetes; however, current detection methods are largely confined to in vitro analysis, making it problematic to obtain dynamic track esterase activity in vivo.

RESULTS

This study designed a fluorescent probe TMN7F, for the accurate diagnosis of diabetes and the dynamic monitoring of insulin therapy. TMN7F employs the dye TMNNH2 as the fluorescent scaffold and heptafluorobutyramide as the esterase-responsive recognition unit. By replacing the conventional ester bond with an amide bond, the probe exhibits markedly improved selective responsiveness to esterases while effectively reducing non-specific interference. TMN7F is capable of sensitively distinguishing differences in esterase activity between hepatocellular carcinoma cells and normal hepatocytes. In vivo imaging experiments with TMN7F showed that fluorescence intensity was markedly greater in diabetic mice than in normal mice and subsequently decreased in an insulin dose-dependent manner following insulin administration. Moreover, the results of ex vivo organ imaging and analyzes of liver and kidney tissue sections obtained using TMN7F corroborated the in vivo imaging findings.

SIGNIFICANCE AND NOVELTY: The probe TMN7F enables real-time tracking of in vivo fluctuations in esterase activity, thereby facilitating the effective monitoring of diabetic pathological progression and the evaluation of insulin therapeutic efficacy.