Bifunctional Ce-MOF nanozyme empowers dual-signal colorimetric assay of antidiabetic α-glucosidase inhibitor drugs.

α-Glucosidase (α-Glu) is a critical target for diabetes therapy, making the discovery of efficient inhibitors important for antidiabetic drug development. Herein, a bifunctional Ce-MOF nanozyme (CeFMA) was synthesized via a one-step coordination assembly at room temperature, which intrinsically integrates oxidase (OXD)-like and laccase (LAC)-like activities. This nanozyme enables a dual-signal colorimetric platform for screening α-Glu inhibitors through two independent catalytic channels. In the OXD channel, CeFMA catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). This process is suppressed by ascorbic acid (AA) generated from α-Glu-triggered hydrolysis of its substrate, and is restored upon inhibition of α-Glu. In the LAC channel, phenol (PhOH) released by α-Glu-mediated hydrolysis of a phenolic glycoside undergoes oxidative coupling with 4-aminoantipyrine catalyzed by CeFMA, producing a red quinone imine product, and inhibition of α-Glu decreases the signal. The two channels operate independently with opposite signal response directions toward inhibitor concentration, enabling a dual-signal readout that can enhance the reliability of inhibitor screening in complex matrices. The platform was successfully applied to evaluate acarbose and oleanolic acid, and further validated in real medicinal herb extracts. This dual-active Ce-MOF nanozyme strategy provides a robust and reliable platform for the screening of natural α-Glu inhibitors, holding promise for antidiabetic drug discovery.