High-entropy alloy nanosheets engineered aptasensor for ultrasensitive detection of pro gastrin releasing peptide in small-cell lung cancer

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.