Determination of Liver Cancer Biomarkers by Surface-Enhanced Raman Scattering Using Gold-Silica Nanoparticles

Abstract

ABSTRACTThe development of rapid, sensitive methods for α-fetoprotein and telomerase is significant because their blood concentrations are related to hepatocellular carcinoma. Therefore, the determination of α-fetoprotein and telomerase may allow the detection of liver cancer. A novel method for the high-yield synthesis of gold-silica alloy core-shell nanoparticles is reported. Gold-silica core-shells prepared by a convenient reduction provided good stability, served as immobilization carriers for the antibodies, and facilitated electron transfer. A simple label-free, three-dimensional hierarchical plasmonic nanoarchitecture was designed for the sensitive surface-enhanced Raman scattering determination of α-fetoprotein and telomerase. The active groups of the gold-silica nanoparticles allowed 4-mercaptobenzoic acid and Nile blue to absorb antibodies and generate a signal. Gold-silica@4-mercaptobenzoic acid and gold-silica@Nile blue were employed in the surface-enhanced Raman scattering immunosensor. When protein biomarkers were present, the sandwich nanoparticles were captured on the substrate, forming a confined plasmonic field, leading to an enhanced electromagnetic field. As a result, the reporter molecules were exposed to a high density of “hot spots” that amplified the Raman signal and enhanced the sensitivity. Under the optimized conditions, the linear dynamic range of the immunosensor was from 0.2 to 22 ng/mL for α-fetoprotein and telomerase. The lowest detectable concentrations were 0.1 and 0.06 ng/mL for α-fetoprotein and telomerase, respectively. The analysis of serum by this method was in good agreement with a standard enzyme-linked immunosorbent assay. This method, based on surface-enhanced Raman scattering of gold-silica, has potential for the determination of biomarkers involved in medical diagnosis and disease monitoring.