A Supersensitive CTC Analysis System Based on Triangular Silver Nanoprisms and SPION with Function of Capture, Enrichment, Detection, and Release

Detection of circulating tumor cells (CTCs) may be applied for diagnosis of early tumors like a liquid biopsy. However, the sensitivity remains a challenge because CTCs are extremely rare in peripheral blood. In this study, we developed a supersensitive CTC analysis system based on triangular silver nanoprisms (AgNPR) and superparamagnetic iron oxide nanoparticles (SPION) with function of capture, enrichment, detection, and release. The AgNPR was encoded with MBA (i.e., 4-mercaptobenzoic acid) and modified with rBSA (i.e., reductive bovine serum albumin) and FA (i.e., folic acid) generating organic/inorganic composite nanoparticle MBA-AgNPR-rBSA-FA, which has the function of surface-enhanced Raman scattering (SERS). The optimized SERS nanoparticles (i.e., MBA3-AgNPR-rBSA4-FA2) can be utilized for CTC detection in blood samples with high sensitivity and specificity, and the LOD (i.e., limit of detection) reaches to five cells per milliliter. In addition, the SPION was also modified with rBSA and FA generating magnetic nanoparticle SPION-rBSA-FA. Our supersensitive CTC analysis system is composed of MBA3-AgNPR-rBSA4-FA2 and SPION-rBSA-FA nanoparticles, which were applied for capture (via interaction between FA and FRα), enrichment (via magnet), and detection (via SERS) of cancer cells from blood samples. The results demonstrate that our supersensitive CTC analysis system has a better sensitivity and specificity than the SERS nanoparticles alone, and the LOD is up to 1 cell/mL. The flow cytometry and LSCM (i.e., laser scanning confocal microscope) results indicate the CTCs captured, enriched, and isolated by our supersensitive CTC analysis system can also be further released (via adding excessive free FA) for further cell expansion and phenotype identification.