Ratiometric fluorescence nanosensor based on CER-assisted CdTe quantum dots for therapeutic drug monitoring of methotrexate

Methotrexate (MTX) is a cornerstone chemotherapeutic agent with a narrow therapeutic index, making therapeutic drug monitoring (TDM) essential to optimize efficacy and prevent severe toxicity. While existing techniques like HPLC and ELISA offer high sensitivity, their complexity, cost, and time requirements can limit rapid clinical decision-making. To address the need for a practical and robust alternative, we developed a novel dual-emission ratiometric fluorescent nanosensor (DERFN) based on cation-exchange reaction (CER)-enhanced CdTe quantum dots. This design prioritizes operational simplicity, rapid analysis, and resilience to matrix interference, achieving reliable MTX detection in the clinically critical concentration range. The sensor exhibits a wide linear response from 0.2 to 120 μM, with a detection limit of 3.75 μM in human serum and excellent recovery rates (100.37–110.71%). While not targeting sub-nanomolar levels required for delayed clearance monitoring, the CER-assisted DERFN platform demonstrates high selectivity, stability, and practicality. It thus presents a promising complementary tool for rapid MTX level assessment in settings where speed, cost-effectiveness, and ease of use are paramount.