Accurate and sensitive determination of sialic acid using three-dimensional Raman imaging based on a background-free SERS strategy

Background Sialic acid (SA) is a significant monosaccharide presented as the terminal moieties of glycoproteins or glycolipids on the cell membrane and closely correlates with various biological and pathological activities, especially in tumor growth and metastasis. It is well known that the overexpression of SA levels could facilitate tumor immune escape, cell proliferation, and angiogenesis. Thus, SA profiling is critical for the early identification and long-term monitoring of tumors. However, it remains limited by the sensitivity and accuracy of the currently available techniques. Results Herein, we proposed a three-dimensional (3D) surface-enhanced Raman scattering (SERS) imaging with a background-free pattern to determine the SA expression at the single-cell level based on a signal amplification strategy. In this study, the target cells were first captured by the phenylboronic acid (PBA) ligands-coated plasmonic gold (pAu) film and further conjugated with benzonitrile-encoded gold SERS nanotags (Au-MBN@Au@PBA) due to the borate bonds, resulting in an enhanced plasmonic structure to generate a wide variety of “hot spots” to improve the SERS signals at 2230 cm −1 channel in the cellular Raman-silent region (1800–2800 cm −1 ). In this study, the 3D SERS imaging enables a deep insight into SA levels, determination of the normal and cancer cell lines, and real-time monitoring of nanoparticle tracking in cancer cells. Significance In this work, the newly prepared PBA ligands possess various capabilities, including modification of SERS nanotags and pAu films, generating good affinity toward SA moieties, and increasing the hydrophilicity of pAu substrate for cell capture. With the assistance of PBA ligands, the pAu film-cell-SERS nanotags sandwich structure was yielded, and the enhanced plasmon coupling was produced, which allows noninvasive, high-precision, and sensitive SA profiling for early tumor diagnosis, glycosylation exploration, and tracking phagocytosis.