High-sensitivity detection of alpha-fetoprotein via an unlabelled fluorescent probe based on switchable AIEE effect of a phenolic compound.

Alpha-fetoprotein (AFP) is a crucial cancer biomarker for the early screening and diagnosis of hepatocellular carcinoma. Here, we report the discovery of a phenolic compound, 5,5'- (anthracene- 9,10-diyl)bis(benzene-1,3-diol) (ABOL), exhibiting typical aggregation-induced emission enhancement (AIEE) effect. ABOL can bind to the nucleobases of the AFP-specific aptamer (AFP-Apt) through hydrogen bonding, π-π stacking, and hydrophobic interactions, forming an ABOL/AFP-Apt complex. After complexation, the free rotation of ABOL's three aromatic rings is hindered, inducing the AIEE effect and subsequently enhancing ABOL's fluorescent intensity. Upon introduction of AFP into the system, the significantly higher binding affinity between AFP-Apt and AFP (compared to that between AFP-Apt and ABOL) causes the dissociation of ABOL from the complex. The return of released ABOL molecules to the solution state leads to the loss of the AIEE effect and reduced fluorescence. Notably, the degree of fluorescence reduction shows a proportional relationship with AFP concentration, enabling both qualitative and quantitative determination of AFP. Experimental results demonstrate a linear correlation between fluorescence reduction and AFP level across a wide range of 6.6-50,000 pg/mL, with an exceptionally low limit of detection (2 pg/mL). The fluorescence probe exhibits high specificity and performs well in AFP detection within human serum samples.