"One stone, two birds": Triple ligand engineered gold nanoclusters with enhanced fluorescence for biomarker detection

Metal nanoclusters (MNCs) have emerged as a promising class of nanomaterials, drawing extensive research focus due to their distinctive properties. As one of the most common MNCs, gold nanoclusters (AuNCs) have been extensively used as signal probes because of their well-defined structures, low toxicity, and adjustable fluorescence characteristics. Nevertheless, the deficiencies of weak intensity and low quantum yield (QY) of AuNCs have hindered their widespread applications. Under these circumstances, the design of innovative strategies for achieving AuNCs with superior emission efficiency remains a critical research priority in this field.

In this work, weakly fluorescent ATT-AuNCs were prepared utilizing 6-aza-2-thiothymine (ATT) as the reducing and protecting agent. The introduction of l-arginine (Arg) and tetrabutylammonium bromide (TBAB) significantly suppresses the intramolecular/intermolecular vibrations and rotations and reduces the nonradiative transition, thereby enabling the QY of ATT-AuNCs to achieve a leap from 1.13 % to 60.49 % (TBAB@Arg/ATT-AuNCs). Notably, a novel sensor was constructed based on TBAB@Arg/ATT-AuNCs for the detection of disease biomarkers. Cu²⁺ and lysozyme (Lys) differentially modulate the fluorescence intensity of TBAB@Arg/ATT-AuNCs based on the dynamic quenching effect and aggregation-induced emission enhancement, respectively. The probe demonstrates linear response ranges of 0-1.32 μM and 1.32-2 μM for Cu²⁺ (detection limit of 0.12 μM), and 6-40 μM for Lys (detection limit of 0.08 μM). Furthermore, this strategy was applied to detect Cu²⁺ and Lys in human serum and urine samples, demonstrating its favorable practicality.

This study develops a novel triple-ligand engineered AuNCs probe (TBAB@Arg/ATT-AuNCs) with enhanced fluorescence and stability for detection of Cu²⁺ and lysozyme, demonstrating excellent analytical performance in real samples. By relying on these observations, the current work not only provides a novel proposal for synthesizing high-performance AuNCs, but also establishes a valuable reference for advancing fluorescence-enhanced nanomaterials in biosensing applications.