Engineered copper-doped carbon dots as peroxidase-mimetic platform for ratiometric fluorescence and colorimetric sensing of anti-cancer drug Ara-C: A new strategy for clinical bioanalysis.

Abstract

Cytarabine (Ara-C) is a frontline chemotherapeutic agent for acute myeloid leukemia and related hematological malignancies; however, its narrow therapeutic window, rapid metabolic clearance, and pronounced interpatient variability necessitate the development of robust analytical tools for precise monitoring in both pharmaceutical formulations and biological fluids. To address this challenge, copper-doped nitrogen carbon dots (Cu-NCDs) were engineered for colorimetric and fluorometric Ara-C detection. The Cu-NCDs integrate peroxidase-mimetic activity with inherent fluorescence, enabling simultaneous colorimetric and ratiometric fluorescence readouts for cross-validated sensing. Copper doping introduced atomically dispersed Cu centers and nitrogen defects, which enhanced catalytic efficiency by accelerating H₂O₂ activation into •OH radicals and facilitating electron transfer, while also amplifying fluorescence intensity. Mechanistically, Ara-C selectively chelated Cu centers, thereby inhibiting catalytic activity, and concurrently modulated the inner filter effect (IFE) with the oxidized OPD product, 2, 3-diaminophenazine (DAP), resulting in distinct dual-mode signal transduction. The platform achieved ultralow detection limits of 8.5 nM (colorimetric) and 4.0 nM (fluorescence), with recovery rates of 98.0-103.0 % in pharmaceutical injections, human serum, and urine. These findings establish Cu-NCDs as a powerful sensing platform with high selectivity, stability, and translational potential for clinical diagnostics, therapeutic drug monitoring, and bioanalytical applications.