摘要： The identification and detection of cancer biomarkers in early stages is an important issue for the therapy of cancer. However, most methods are time-consuming, limited sensing sensitivity and specificity. In this work, we prepared a novel plasmonic multilayered core–shell-satellite nanostructure (Au@Ag@SiO2-AuNP) consisting of an gold nanosphere with silver coating core (Au@Ag), an ultrathin continuous silica (SiO2) shell and high coverage of gold nanospheres (AuNPs) satellites. Au@Ag core is prominent surface enhanced Raman scattering (SERS) platform and the thin SiO2 layer exhibits a long-range plasmon coupling between Au@Ag core to AuNPs satellites further leading to enhanced Raman scattering. Meanwhile, the outer AuNPs satellites have a high biocompatibility and long-term stability. Combining the above advantages, the well-designed metallic nanoassemblies would be a promising candidate for SERS-based applications in biochemistry. For specific detection of alpha-fetoprotein (AFP), we utilized the SERS-active core-shell-satellite nanostructures modified with AFP antibody as immune probes and nitrocellulose membrane (NC) stabilized captured anti-AFP antibodies as solid substrate. To improve the detection performance, we further systematically optimized the parameters, including silver coating thickness of Au@Ag core, the density and size of satellite AuNPs. Under the optimized conditions, AFP could be detected by the SERS-based sandwich immunoassay with an ultralow detection limit of 0.3 fg/mL, and the method exhibited a wide linear response from 1 fg/mL to 1 ng/mL. The limit of detection (LOD) was considerably lower than conventional methods in literature. This work relies on the unique Au@Ag@SiO2-AuNP nanostructures as immune probe develops a new outlook for the application of multilayered nanoassemblies and demonstrates the great potential in early tumor markers detection.