Potassium-doped amino acid-rich carbon dots for real-time detection of methotrexate: a novel PL enhancement-based point-of-care sensor

Narrow therapeutic index (NTI) drugs are critical for managing serious conditions, but demand constant monitoring due to their narrow margin and risk of inducing nutrient deficiencies. Methotrexate (MTX), for instance, can deplete folate and induce hypokalemia, leading to complications if unmonitored. Photoluminescence (PL)-based sensors offer real-time monitoring potential, yet existing PL quenching models face poor LOD, low linearity, and photo-bleaching. This manuscript aims to develop a sensitive and reliable PL-based sensing strategy that overcomes these limitations by leveraging MTX-induced potassium deficiency to enhance PL response through stable complex formation. To achieve this, potassium-doped, carboxylic- and amide-rich carbon dots (CDs) were synthesized using amino acid-rich palm wine, offering a unique, unexplored approach. These CDs form a stable complex with MTX, resulting in PL enhancement. DFT simulations and comprehensive analyses were performed to delineate the PL enhancement mechanism and evaluate the sensing performance. The synthesized CDs exhibited excellent sensitivity towards MTX, showing a strong linear relationship over a wide concentration range of 1-3000 ppb, and a low LOD of 1.16 ppb (2.55 nM). The selectivity and interference studies confirmed the sensing probes’ robustness in complex environments. The sensing probe quantified MTX in pharmaceutical tablets and cancer patients’ plasma with excellent accuracy. A smartphone-assisted point-of-care (POC) device integrated with the probe demonstrated remarkable performance and suitability in resource-limited settings. This study introduces a CD-based sensing platform in which potassium-doped surface chemistry and CD-MTX complexation enable sensitive, selective, and real-time MTX detection. This CD-based sensor strategy, leveraging NTI-induced deficiencies is extendable to other NTI drugs, as demonstrated herein.