Gold concave cubic nanoparticle-based SERS sensor for sensitive detection of osteoporosis-associated SA-β-gal

β-Galactosidase (SA-β-gal) is a key marker of cell aging and abnormal apoptosis. Its overexpression is closely related to osteoporosis (OP) and other cell aging related diseases. In this study, a novel surface enhanced Raman scattering (SERS) sensor based on gold concave cubic nanoparticles (CCAuNPs) was prepared. This sensor featured a typical sandwich structure that enabled the sensitive detection of SA-β-gal in serum through a cascade of enzyme-mediated release and light-coupled reactions. In the detection process, as the link between the active substrate and the SERS probe, the β-galactoside bond in the molecule of lactose was specifically recognized and cut off by SA-β-gal, which led to the separation of the SERS probe which was tightly bound to the surface of the active substrate. This was specifically manifested as a decrease in the SERS intensity of the characteristic peak at 1139 cm^-1 of 4,4'-dimethylbenzothiazole (DMAB), formed by the laser irradiation of 4-aminothiophenol (4-ATP). This SERS sensor demonstrated excellent detection performance, exhibiting high selectivity for the target analyte, good reproducibility, and extremely high sensitivity, with a limit of detection (LOD) as low as 1.85 × 10^-5 U mL^-1. The accuracy and clinical utility of this sensor were further validated using enzyme-linked immunosorbent assay (ELISA), with relative errors of less than 10%. The SERS sensor proposed in this study offers a new SERS-based approach for the clinical screening of OP.