CuAg NCs with AIE Effect Coordinated by Ce3+ as a Novel Fluorescent Probe for the screening of ATP inhibiting drugs.

BACKGROUND

In recent years, bimetallic nanoclusters (NCs) have emerged as promising functional materials, particularly those exhibiting aggregation-induced emission (AIE) properties. Compared to single-metal systems or organic AIE fluorophores, they offer enhanced fluorescence, superior stability, straightforward synthesis, and excellent biocompatibility. This has enabled them to attract considerable attention in the field of chemical sensing and bioimaging. Specifically, adenosine triphosphate (ATP) serves as a critical biomarker, and the development of sensitive fluorescent probes for its detection is of significant importance in biomedical research and clinical diagnostics.

RESULTS

This study developed a mitochondrial-targeted fluorescent probe based on Ce3+- coordinated copper-silver bimetallic nanoclusters (CuAg NCs), designed for selective ATP recognition and ATP-inhibiting drugs screening. The AIE-active CuAg NCs were synthesized via a facile approach using l-glutathione (GSH) as both reducing agent and stabilizing ligand. Upon addition of Ce3+, the quantum yields (QYs) increased from 0.60% to 22.64%. This attributed to the suppression of non-radiative relaxation pathways in the excited states through coordination interaction between Ce3+ and carboxyl groups (-COOH) of surface-anchored GSH ligands. Leveraging the coordination between Ce3+ and the triphosphate moiety of ATP, a turn-off fluorescent probe was constructed, demonstrating a linear response within 1-30 μM and a detection limit of 0.105 μM. Owing to its biocompatibility and inherent mitochondrial-targeting ability, it enabled effective intracellular ATP monitoring. In HepG2 cells, fluorescence intensity showed clear dose-dependence upon treatment with ATP-activator (Glimepiride) and ATP-inhibitor (Imatinib).

SIGNIFICANCE AND NOVELTY: This work not only presents a sensitive and selective probe for ATP determination but also establishes a versatile platform for real-time tracking of intracellular ATP levels and screening of ATP-modulating drugs. The proposed design strategy based on metal-coordination enhanced bimetallic NCs offers a novel pathway for developing organelle-targeted functional probes, highlighting its potential in biomedical sensing and pharmacological research.