Detection of circulating tumor cells based on improved SERS-active magnetic nanoparticles

摘要

Cancer cells can shed into the vasculature from tumors and form circulating tumor cells (CTCs), which circulate in the blood stream. Surface-enhanced Raman scattering (SERS) is a very suitable technology for CTC detection due to its high sensitivity. In this study, improved SERS-active magnetic nanoparticles were designed and constructed for CTC detection. Poly(ethyleneimine) (PEI)-stabilized superparamagnetic iron oxide nanoparticles (SPION-PEI) were synthesized by a solvothermal method. Negatively charged gold nanoparticles (AuNPs) were then self-assembled in situ on the surface of SPION-PEI. The obtained SPION-PEI@AuNPs were modified with 4-mercaptobenzoic acid (MBA, a Raman reporter molecule) and FA-conjugated rBSA (rBSA-FA) via Au–S bonds resulting in the composite nanoparticles SPION-PEI@AuNPs-MBA-rBSA-FA (SERS-active magnetic nanoparticles). SPION-PEI@AuNPs-MBA-rBSA-FA nanoparticles showed good specificity to HeLa cells and the limit of detection (LOD) was 1 cell per mL of blood, which is the best among the reported values. The linear relationship between the concentration of cancer cells and the SERS intensity was utilized for quantitative measurement of CTCs. The SPION-PEI@AuNPs-MBA-rBSA-FA was released from the CTCs via culturing with excess folic acid, and the released CTCs were further cultured for expansion and molecular phenotype analysis. The concentrations of CTCs in the blood of two first-stage clinical patients with cervical cancer were measured to be 6 ± 2 cells per 10 mL or 13 ± 5 cells per 10 mL by our SERS-active magnetic nanoparticles.