Effective Isolation, Label and Release of Multitype Circulating Tumor Cells Base on CdSe/ZnS Quantum Dots and Dual-antibody Modified Magnetic Nanoparticles

The identification and dynamic monitoring of circulating tumor cells (CTCs) are of vital importance for clinical diagnosis, prognosis evaluation and personalized therapy of cancer patients. However, during the process of tumor metastasis, epithelial-mesenchymal transition (EMT) may occur, resulting in the loss of the expression of surface protein markers on tumor cells, which makes it difficult to effectively isolate CTCs using traditional enrichment strategies based on a single epithelial characteristic marker. In addition, the immunostaining methods commonly used to identify CTCs require cell fixation, which can only provide limited information on the number of CTCs, thus limiting further biological research on CTCs. To address these issues, this study prepared magnetite nanoparticles (MNPs) with a core-shell structure to enable enrichment, purification and identification of different types of CTCs. The outer layer was decorated with CdSe/ZnS quantum dots (QDs) to enable labeling, while the subsequently modified gelatin layer could suppress non-specific adhesion of blood cells with good performance of thermos-sensitivity for CTC release. Finally, two types of antibodies targeting epithelial cell adhesion molecule (EpCAM) and N-cadherin were modified on the surface of MNPs, creating a simple and efficient platform for CTCs enrichment, labeling and release. The capture efficiency of the platform for epithelial and mesenchymal CTCs reached 85.5% and 92.4%, respectively. In addition, the layer of QDs assembled on the surface of MNPs enabled labeling and identification of target cells without cell fixation and immune-staining processes. After a short time of incubation at 37 & DEG;C, 88% of the captured cells were successfully released due to the conformation change of gelatin molecules on the surface of MNPs, with a cell viability of 94.9%. The platform developed here provided a new strategy for CTC detection in clinical application.