College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun, Jilin130012, China.
Anal Chem. 2023 Feb 14;95(6):3414-3422. doi: 10.1021/acs.analchem.2c05098. Epub 2023 Jan 30.
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 Zn 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 ( = 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.
碱性磷酸酶（ALP）广泛存在于人体中，是一种重要的生物标志物。已经进行了许多 ALP 检测研究，由于在 ALP 的存在下可以从抗坏血酸 2-磷酸（AA2P）水解中产生抗坏血酸（AA），因此 AA 通常被用作传感器中的还原成分来监测 ALP 水平。然而，众所周知，AA 是一种强还原剂，很容易被氧化。氧化 AA 和还原 AA 反应之间的歧化导致产生具有单电子的 AA 自由基，这可能导致测定结果不准确。为了解决这个问题，我们合成了核壳金属有机骨架传感器（PATP-Au@ZIF-8 NP），并将其用作具有自触发控制磷酸盐离子（Pi）的灵敏和准确的 ALP 检测传感器，以避免使用 AA 作为还原成分的方法的潜在不准确性。通过在金纳米粒子（Au NPs）的表面建立物理壳，传感器不仅可以消除等离子体暴露引起的金属纳米粒子的随机组装，还可以产生由 ALP 引起的 Pi 的自触发。Pi 可以通过与 Zn 配位来分解 ZIF-8，从而破坏制备的 PAZ NPs 的 ZIF-8 壳结构。Au NPs 被释放并随后聚集，从而导致 SERS“热点”区域增加。发现 SERS 信号的增强与从 ALP 触发的水解释放的 Pi 水平直接相关。该策略的响应在 ALP 浓度范围为 0.1 至 150 mU/mL（ = 0.996）内呈线性，检测限为 0.03 mU/mL。最后，该策略用于评估 ALP 抑制剂，并且证明了开发的 SERS 策略用于快速和选择性分析人血清中 ALP 的可能性。
