A novel near-infrared-II fluorescence probe for serum albumin biosensing and site-binding mechanism study

Abnormal albumin levels are predictors of nephropathy, liver cirrhosis, coronary heart disease, and diabetes. Sensitive and rapid detection of endogenous albumin is of great significance to disease diagnosis and new drug discovery. Here, the first near-infrared-II fluorescence probe for albumin was developed. Based on the remarkable fluorescence enhancement induced by albumin, both human serum albumin (HSA) and bovine serum albumin (BSA) were quantified in several minutes. The limit of detection for albumin in urine samples is as low as 50 nM, which meets the requirement well for clinical analysis. The fluorescence imaging of drug-induced albumin in living cells verified strong capability for the probe to monitor the endogenous albumin. The site-binding mechanism between the probe and albumin was investigated via Job's plots analysis, drug substitution assays, and molecular docking. The NIR-II probe exhibits a specific and high-affinity binding (K_b=5.26×10¹¹ M⁻¹) with albumin, which enabled a further determination of trypsin and a protease inhibitor. This novel versatile biosensor provides a promising strategy for on-site evaluating of endogenous albumin for clinical diagnostics and drug screening.