Specific and quantitative detection of albumin in biological fluids by tetrazolate-functionalized water-soluble AIEgens.

Abstract

The analysis of albumin has clinical significance in diagnostic tests and obvious value to researches on the albumin-mediated drug delivery and therapeutics. The present immunoassay, instrumental techniques, and colorimetric methods for albumin detection are either expensive, troublesome or insensitive. Herein, a class of water-soluble tetrazolate-functionalized derivatives with aggregation-induced emission (AIE) characteristics are introduced as novel fluorescent probes for albumin detection. They can be selectively lighted up by site-specific binding with albumin. The resulting albumin fluorescent assay exhibits a low detection limit (0.21 nM), high robustness in aqueous buffer ( pH = 6~9), and a broad tunable linear dynamic range (0.02~3000 mg/L) for quantification. The tetrazolate functionality endows the probes with a superior water solubility ( > 0.01 M) and a high binding affinity to albumin (KD = 0.25 µM). To explore the detection mechanism, three unique polar binding sites on albumin are computationally identified, where the multivalent tetrazolate-lysine interactions contribute to the tight binding and restriction of molecular motion of the AIE probes. The key role of lysine residues is verified by the detection of poly-L-lysine. Eventually, we applied the fluorogenic method to quantify urinary albumin in clinical samples and found it a feasible and practical strategy for albumin analysis in complex biological fluids.