Toward Bioreceptor-Free Nanozyme Sensing: Matched Interaction and Ligand-Modulated Phosphatase-Mimetic Activity Enable Anti-Interference and Sensitive Detection of Quinolones in Dairy Products

Compared with oxidoreductase mimics, hydrolase-like nanozymes can circumvent the interference from redox species in real matrices, exhibiting unique superiority for biochemical sensing, but insufficient catalytic efficiency and lack of specific response to targets when no bioreceptor (aptamer, antibody, etc.) is employed greatly restrict their advanced analytical applications. To solve this predicament, here we employed a ligand engineering strategy to modulate the phosphatase-mimetic activity of Nd(III)-coordinated phenylboronic acid (PBA) derivatives and achieved anti-interference and sensitive detection of quinolone antibiotics in dairy products based on matched interaction and ligand-optimized catalytic efficiency. By tailoring the ortho-substituted PBA ligand, precise activity control was obtained through adjusting surface Lewis acidity and substrate adsorption jointly. Quinolones could specifically suppress the activity of Nd-PBA via strong hydrogen bonding, π-π stacking, and coordination interactions, allowing the nanozyme to function as both recognition unit and signal transducer without the need for external bioreceptors. According to the principle, high-performance sensing of ciprofloxacin as a quinolone model was validated. By leveraging the synergy of specific interaction and hydrolase-mimicking catalytic nature, the established approach exhibited good anti-interference capability in complex matrices. The ligand-modulated catalytic activity provided sufficient sensitivity for detecting the analyte in dairy products. Our attribution not only develops a new hydrolase mimic with engineerable phosphatase-like catalytic characteristics via ligand programming but also offers a rarely explored approach for selectively detecting quinolone antibiotic residues, inspiring future design of bioreceptor-free nanozyme sensing systems for broader applications.