A Strategy for the Determination of Alkaline Phosphatase Based on the Self-Triggered Degradation of Metal–Organic Frameworks by Phosphate

Alkaline phosphatase (ALP) is widely present in the human body and is an important biomarker. Numerous ALP detection studies have been carried out, and ascorbic acid (AA) is often used as the reducing component in the sensors to monitor ALP levels since it can be produced from ascorbic acid 2-phosphate (AA2P) hydrolysis in the presence of ALP. However, it is well-known that AA is a strong reducing agent and can be easily oxidized. The disproportion between oxidized AA and reduced AA reactions results in the generation of AA free radicals with single electrons that may lead to inaccurate results in assays. To solve this problem, we synthesized a core-shell metal-organic framework sensor (PATP-Au@ZIF-8 NP) and used it as a sensitive and accurate ALP detection sensor with self-triggered control of phosphate ions (Pi) to avoid the potential inaccuracy of the method that uses AA as the reducing component. By establishing a physical shell on the surface of the gold nanoparticles (Au NPs), the sensor not only can eliminate the random assembly of metal nanoparticles caused by plasma exposure but also can generate self-triggering of Pi caused by ALP. Pi can decompose ZIF-8 through coordination with Zn²⁺ and thus can destroy the ZIF-8 shell structure of the prepared PAZ NPs. Au NPs are released and then become aggregated, in turn causing the SERS "hot spot" area to increase. The enhancement of the SERS signals was found to be directly associated with the level of Pi released from ALP-triggered hydrolysis. The response of the strategy was linear at ALP concentrations ranging from 0.1 to 150 mU/mL (r = 0.996) with a detection limit of 0.03 mU/mL. Lastly, the developed strategy was employed in the evaluation of ALP inhibitors, and the possibility to implement the developed SERS strategy for rapid and selective analysis of ALP in human serum was demonstrated.