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 research studies 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 is 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 (K D = 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 the molecular motion of the AIE probes. The key role of lysine residues is verified by the detection of poly-l-lysine. Moreover, 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.

Detection of Urinary Albumin Using a “Turn‐on” Fluorescent Probe with Aggregation‐Induced Emission Characteristics

“…Based on our previous research, AIE fluorogens (AIEgens) with periphery‐charged groups including sulfonate, carboxylate, trialkyl‐ammonium, pyridinium, and tetrazolium groups, may have fluorescence enhancements upon binding with HSA [5c,13] . These functional groups facilitate AIEgens to dissolve in water, thus exhibiting weak fluorescence.…”

“…1,3‐Indanedione was obtained from Alfa Aesar. Probes BSPOTPE and TPE‐4TA were synthesized according to previously publications [11,13] . 1 H (400 MHz) & 13 C NMR (100 MHz) spectra were acquired on Agilent MR400 or Agilent DD2 instrument.…”

“…Recently, Tu et al. reported another TPE derivative, TPE‐4TA , for specific and quantitative detection of HSA [13] . In this work, tetrazolate, which has a strong binding affinity toward HSA, was used as the targeting moiety.…”

Detection of biomarkers in body fluids using bioprobes based on aggregation-induced emission fluorogens

“…This study also used human urine samples for clinical diagnosis, indicating satisfactory accuracy and linearity. 22…”

An Intelligent AIEgen with Nonmonotonic Multi-Responses to Multi-Stimuli

“…8 Fluorescent probes with multifunctionality (n/1) are also explored. 9,10 However, the (n/n) system with nonmonotonic modes is seldom reported (Fig. 1).…”