Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid progression, early metastasis, and poor prognosis. These features highlight the urgent need for ultrasensitive and non-invasive diagnostic methods. Pro-gastrin-releasing peptide (ProGRP) has emerged as a highly specific biomarker for SCLC. However, existing detection techniques are often limited by long assay times and insufficient sensitivity. In this study, we developed a new electrochemical aptasensor based on two-dimensional high-entropy alloy nanosheets (HEANSs) for ultra-precise detection of ProGRP. The HEANSs were synthesized via a salt-templated method, which enabled precise control over composition, enhanced catalytic activity due to lattice distortion, and a uniform nanosheet morphology with high surface area. The HEANSs were functionalized with polydopamine (PDA), thereby introducing a variety of reactive functional groups that improved biocompatibility and markedly enhanced the efficiency of aptamer immobilization. This synergistic design achieved a broad linear detection range from 10 pg/mL to 100 μg/mL, an ultra-low limit of detection (LOD) of 0.874 pg/mL (S/N = 3), and excellent reproducibility with a relative standard deviation (RSD) of 1.78%. Moreover, the sensor retained 3.75% of its initial signal after nine days of storage, demonstrating exceptional stability. This pioneering HEANSs@PDA-based aptasensor provides a scalable and versatile platform for ultrasensitive biomarker detection, holding significant potential for early cancer diagnosis, real-time clinical monitoring, and precision medicine applications.

Nanozymes are nanomaterials with enzyme-mimicking catalytic activity. Compared to natural enzymes, nanozymes show various properties such as easy to manufacture, stable, adjustable, and inexpensive. Nanozymes play key roles in biosensing, biocatalysis, and disease treatment. As an important kind of nanozymes, metal-organic framework (MOF)-based nanozymes are receiving a lot of attention due to their structural properties and composition. Rationally developing MOF with enzymes-like catalytic properties has opened new perspectives in biosensing. This review summarizes the up-to-date developments in synthesizing two-dimensional and three-dimensional MOF-based nanozymes and their applications in biosensing. Firstly, classification of nanozymes obtained by MOFs is categorized, and different properties of MOF-based nanozymes are described. Then, the distinctive applications of MOF-based nanozymes in identifying various analytes are thoroughly summarized. Finally, the recent challenges and progressive directions in this area are highlighted.