A fluorescent sensor recognized by the FA1 site for highly sensitive detection of HSA

Human serum albumin (HSA), as the most abundant protein in blood plasma, plays a crucial role in many physiological processes. The abnormal HSA level in serum or in urine is often associated with various diseases. Therefore, to achieve highly sensitive and selective quantification of HSA is of great importance for disease diagnosis and preventive medicine. Herein, an HSA-selective light-up fluorescent sensor, DCM-ML, was successfully developed for quantitative detection of HSA. DCM-ML exhibited good (photo-) stability and strong fluorescence enhancement around 630 nm in the presence of HSA in complex samples containing numerous biological analytes. Upon addition of HSA into DCM-ML containing solution, a good linear relationship (R² > 0.99) between the fluorescence intensity of DCM-ML and HSA concentration from 0 to 0.08 mg/mL was obtained with the detection limit of 0.25 μg/mL. The sensing mechanism of the sensor towards HSA was demonstrated to be via recognition in the fatty acid site 1 (FA1), instead of the most reported binding sites (Sudlow I and II) in HSA, for the first time, by both the displacement experiments and molecular docking simulation. Thus, DCM-ML can also be assumed as a potential FA1 site-binding marker for examining drugs binding to the FA1 site in HSA. At last, the utilization of sensor DCM-ML for quantification and validation of HSA in urine samples and cell culture medium was effectively demonstrated. Therefore, the development of DCM-ML should find great application potentials in the fields of analytical chemistry and clinical medicine as a highly sensitive HSA sensor.