Detection Of Circulating Tumor Cells Based On Lanthanide-doped Nanoprobes

Circulating tumor cells are cells released into the circulatory system by tumor in situ and metastasis.Since Circulating tumor cells have been found in peripheral blood of cancer patients for the first time by Thomas Ashworth in 1869,there has been increasing evidence that circulating tumor cells are associated with the metastasis of cancer.Metastasis is known to be the leading cause of death in patients.Therefore,circulating tumor cells have gradually attracted people's attention and become a research hotspot.Circulating tumor cells detection can be used as a"liquid biopsy"by obtaining patient blood samples at any time,and to guide clinical development of medical plans,judgment of patients'prognosis,evaluation of curative effect,etc.,which has unique advantages for real-time individualized treatment of cancer patients.However,the number of circulating tumor cells is very rare and can only be counted in the single digits in blood,which poses a great challenge for its detection.Therefore,the development of stable,sensitive and specific detection methods is the key to carry out circulating tumor cells related research.In our previous work,a new dissolution-enhanced luminescent bioassay?DELBA?has been developed.Moreover,it has been proved that DELBA method has good sensitivity in the detection of tumor markers,such as carcino-embryonic antigen?CEA?,prostate specific antigen?PSA?,alpha fetoprotein?AFP?or cancer biomarker microRNA.In this paper,anti-EpCAM antibody were selected and used together with NaEuF₄nanoparticles to construct a biological probe specifically detecting circulating tumor cells.Therefore,an ultra-sensitive detection platform for circulating tumor cells was established by using the highly sensitive DELBA biological detection method.The linear detection range was 2-1024 circulating tumor cells,and the detection limit was 1 circulating tumor cell in whole blood without any enrichment process.Finally,we tested the potential clinical application of the platform with blood samples from healthy and clinical breast cancer patients.The results showed that no circulating tumor cells were detected in 4 healthy samples,and the positive detection rate of circulating tumor cells was as high as 93.9% in 15 breast cancer patients.Through further analysis,it was found that there was a significant correlation between the disease progression and the number of circulating tumor cells.This indicates that our circulating tumor cell detection platform has potential clinical application,and provides an detection program for the detection of circulating tumor cells in clinical cancer patients for the detection,monitoring and treatment program adjustment.