Time-resolved luminescent nanoprobes based on lanthanide nucleotide self-assemblies for alkaline phosphatase detection

Currently, enzyme-responsive nanomaterials have shown great promise in prognosis or diagnosis of disease biomarker. However, the great obstacle for conventional enzyme-responsive nanomaterials frequently lies in autofluorescence interference, poor monodispersity, uncontrollable size and morphology, low optical stability, and biotoxicity, which fundamentally impede their practical application in biological systems. To overcome these deficiencies, we proposed a novel strategy for reliable and precise detection of an enzyme disease biomarker, alkaline phosphatase (ALP), through lanthanide (Ln³⁺) nucleotide nanoparticles (LNNPs) with extremely improved monodispersity and uniformity, which were achieved by the coordination self-assembly between ATP and Ln³⁺ inside micellar nanoreactor. Specifically, for ATP-Ce/Tb LNNPs, highly improved photoluminescence (PL) emission of Tb³⁺ can be achieved via efficient Ce³⁺ sensitization. We demonstrated that ALP could specifically cleave the phosphorus–oxygen (P–O) bonds of ATP and result in the collapse of ATP-Ce/Tb scaffold, finally leading to the PL quenching of Tb³⁺. By taking advantage of time-resolved (TR) PL technique, the fabricated ATP-Ce/Tb LNNPs presented superior selectivity and sensitivity for the ALP bioassay in complicated serum samples, thus revealing the great potential of ATP-Ce/Tb LNNPs in the areas of ALP-related disease prognosis and diagnosis.