Huang_2025_Anal.Chem_97_16142

Acetylcholinesterase (AChE), one of nature's most efficient enzymes, plays a crucial role in neural signal transduction and the restoration of tissue homeostasis with implications in the development of neurodegenerative diseases. Conventional methods for detecting AChE mainly rely on its catalytic activity. Herein, we present an approach for AChE detection based on its chiral binding with photoluminescent carbon dots (CDs) with rich chiral cysteine residues (L/D-CDs), synthesized via a general hydrothermal route. Interestingly, L-CDs, despite being synthesized under the same conditions as D-CDs, exhibited a stronger specific binding affinity for AChE than D-CDs through electrostatic interactions, attributed to the amphiphilic nature of AChE, leading to enhanced photoluminescence near the isoelectric point of AChE at 6.50. The enhanced photoluminescence intensity of L-CDs showed a linear correlation with AChE concentrations over the range of 200-4500 mU/mL with a detection limit of 20 mU/mL. Meanwhile, by leveraging the selective recognition of AChE by L-CDs, we applied the probe to distinguish between liver cancer tissues and adjacent nontumor tissues. The results demonstrated that, due to the reduced AChE content in liver cancer tissues, the fluorescence intensity was significantly lower than that in adjacent nontumor tissues. Our findings highlight the potential of CDs rich in chiral residuals as optical probes for biosensing and imaging applications based on biomolecular recognition.