Activatable fluorescent nanosensor for real-time detection and intracellular imaging of histone deacetylase 1

A novel signal-switchable fluorescent biosensing platform was rationally developed based on oxidized single-walled carbon nanohorns (oxSWCNHs) and FAM-labeled peptide probes for the highly sensitive detection, activity evaluation, and intracellular bioimaging of histone deacetylase 1 (HDAC1). The FAM-modified peptide substrate could be tightly adsorbed on the oxSWCNHs. In the presence of HDAC1, the specific deacetylation of acetyl-lysine residues initiated the sequential enzymatic cleavage reaction triggered by carboxypeptidase Y (CPY), which led to the detachment of fluorophores from oxSWCNHs and the obvious recovery of fluorescence signals. Under optimized experimental conditions, the constructed biosensor exhibited excellent sensing performance toward HDAC1 with a low detection limit of 1.4 ng/mL. Meanwhile, the sensing system was effectively utilized to precisely detect HDAC1 in the serum of humans, quantitatively assess the inhibitory effect of trichostatin A (TSA), and achieve intracellular fluorescence imaging of endogenous HDAC1 in living cells. Featuring high sensitivity, favorable specificity, and simple operation, this fluorescent sensing strategy provides a promising and universal tool for clinical HDAC1 analysis, disease-related research and inhibitor screening.