Rapid and efficient isolation and detection of circulating tumor cells based on ZnS:Mn2+ quantum dots and magnetic nanocomposites

Abstract

Rapid and non-destructive detection of circulating tumor cells (CTCs) with no disruption of their functions is of great significance for clinical tumor therapy. However, many existing methods for CTC detection commonly rely on conventional three-color immunofluorescence identification, which damages CTCs and easily causes loss of cells. Here, we employed a method to simultaneously capture and authenticate CTCs based on immunonanocomposites (ZnS:Mn2+ QDs and Fe3O4/SiO2) equipped with permanent fluorescent and magnetic properties. A multifunctional nanocomposite was synthesized by encapsulating ZnS:Mn2+ quantum dots (QDs) and Fe3O4 nanoparticles into SiO2 nanospheres and bio-conjugating tumor-specific anti-EpCAM antibodies onto the surface. The resulting nanocomposite had a high tumor cell binding ability, and the Fe3O4 nanoparticles had a rapid magnetic response that enabled capture of circulating tumor cells from patients' blood within minutes. In addition, the cell-immunonanocomposites complexes could be directly recognized by the yellow-orange light emitted by the ZnS:Mn2+ quantum dots, thus labeling cells without utilizing the complicated and destructive procedures involved in traditional CTCs identification. We successfully achieved a high capture efficiency of up to 90.8%, and the specific fluorescence labeling of CTCs was realized in 9 clinical breast cancer patients’ samples. Furthermore, this simple, convenient and cell-friendly approach is significant for solving the problems of cell viability and enables non-destructive CTC detection, which marks an advance in cancer treatment and clinical applications.