Improved SERS-Active Nanoparticles with Various Shapes for CTC Detection without Enrichment Process with Supersensitivity and High Specificity

Circulating tumor cells (CTCs) have received more and more attention in medical biology and clinical practice, especially diagnosis, prognosis, and cancer treatment monitoring. The detection of CTCs within the large number of healthy blood cells is a big challenge due to their rarity, which requires a detection method with supersensitivity and high specificity. In this study, we developed three kinds of new nanoparticles with the function of surface-enhanced Raman scattering (SERS) based on spherical gold nanoparticles (AuNPs), gold nanorods (AuNRs), and gold nanostars (AuNSs) with similar particle size, similar modifications, and different shapes for CTC detection without an enrichment process from the blood. The nanoparticles possess strong SERS signal due to modification of 4-mercaptobenzoic acid (4-MBA) (i.e., Raman reporter molecule), possess excellent specificity due to stabilization of reductive bovine serum albumin (rBSA) to reduce the nonspecific catching or uptake by healthy cells in blood, and possess high sensitivity due to conjugation of folic acid (FA) (i.e., a targeted ligand) to identify CTCs. Under the optimized experimental conditions, the results of detection demonstrate that these nanoparticles could all be utilized for CTC detection without enrichment process from the blood with high specificity, and the AuNS-MBA-rBSA-FA is the best one due to its supersensitivity, whose limit of detection (i.e., 1 cell/mL) is much lower than the currently reported lowest value (5 cells/mL).