FRET-triggered fluorescence switching: a g-CNQDs/Cu-TCPP "turn-on" aptasensor for ultrasensitive GP73 detection

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, and early diagnosis is crucial. Golgi protein 73 (GP73) has emerged as a promising serum biomarker for HCC. However, current detection methods often fail to meet routine screening requirements due to limitations in sensitivity and operational simplicity. To address these challenges, we have developed a novel fluorescent aptamer-based sensor for highly sensitive GP73 detection based on the fluorescence resonance energy transfer (FRET) mechanism between graphitic carbon nitride quantum dots (g-CNQDs) and a copper-based metal-organic framework (Cu-TCPP). g-CNQDs were covalently conjugated with a GP73-specific aptamer to serve as the fluorescent donor, while two-dimensional Cu-TCPP nanosheets acted as the efficient acceptors. Fluorescence was quenched upon donor-acceptor interaction via FRET. In the presence of GP73, aptamer-target binding disrupted FRET interaction, separating the donor from the acceptor and restoring fluorescence in a concentration-dependent manner. Under optimal conditions, the sensor exhibited excellent linearity over a concentration range 1.0-225.0 ng mL⁻¹, with a detection limit as low as 0.907 ng mL⁻¹. Recoveries for spiked human serum samples ranged from 95.96% to 103.85%, with relative standard deviations (RSDs) of 0.38%-5.48%. The developed aptamer sensor demonstrated excellent sensitivity, selectivity, and stability, providing a powerful tool for early HCC diagnosis and offering strong potential for real-time analytical applications.