Accurate quantitative detection of cell surface sialic acids with a background-free SERS probe

Sialic acid (SA) is a special monosaccharide widely distributed at the termini of sugar chains on the cell surface, and its expression level is closely connected with various biological and pathological processes. Therefore, accurate quantitative detection of SA on cancer cell surface is of great significance for clinical diagnosis and therapy. Here, we developed a whole-surface accessible method of accurate SERS quantification of SA level on a single cell, in which silver nanoparticles functionalized with 4-mercaptophenylboric acid and 4-mercaptobenzenitrile was used as the background-free SERS probe. The cyano group on the nanoprobe showed a unique Raman shift at 2232 cm^-1, where most of the biological samples have no Raman response. Meanwhile, the boronic acid group had high specificity to SA molecules at physiological pH. The expression level of SA can be accurately quantitated on the basis of the CN Raman signal. The average number of expressed SA molecules on the surface of a single HeLa cell was 4.6 × 10⁷. And SERS imaging of a single cell was achieved at 2232 cm^-1 without biological interference. We evaluated SA expression level on the surface of different cancer cells and dynamically monitored SA expression under the influence of drugs. The proposed approach is accurate as well as sensitive for background-free quantification of SA on cell surface, which is promising for revealing the relationship between tumors and cell surface glycosylation.