Angelw: the first direct detection of circulating tumor cells in whole blood based on rare earth nanoprobes

Circulating tumor cell (CTC) is a kind of tumor cell which is separated from the primary tumor or metastasis and dissociated into peripheral blood It is easy to cause tumor recurrence or metastasis and significantly increase the treatment difficulty and death risk of tumor patients Therefore, the effective detection of CTC is of great significance to the early diagnosis, prognosis judgment and curative effect monitoring of tumor However, due to the low content of CTC in the blood, the traditional two-step analysis method based on "enrichment detection" has the disadvantages of cumbersome operation, low sensitivity and easy to produce false negative How to realize the high sensitive and direct detection of CTC in whole blood is a major challenge in the field of tumor diagnosis and treatment Chen Zhuo, the State Key Laboratory of structural chemistry of Fujian Institute of physical architecture, and Chen Xueyuan, the Key Laboratory of functional nanostructure design and assembly of Chinese Academy of Sciences supported by NSFC, the strategic leading science and technology project of Chinese Academy of Sciences, the innovation international team of Chinese Academy of Sciences and the introduction of high-level entrepreneurship and innovation talents in Fujian Province Dr Song Xiaorong and master Guo Han, the winners of the excellent postdoctoral program jointly funded by "take the lead in action", have realized the high sensitive and direct detection of CTC in whole blood for the first time by using time-resolved rare earth nanofluorescence probes The rare earth Nanofluorescent probe can target the highly expressed epidermal cell adhesion molecule (EpCAM) on the surface of epithelial tumor cells to realize the specific and efficient recognition of CTC With the help of the solution enhanced fluorescence amplification technology of rare earth nanoparticles (naeuf 4) and the long-lived europium ion complex red fluorescence signal, the rare earth nanoprobe can effectively overcome the interference of short-lived background fluorescence signal in complex blood samples, greatly improve the sensitivity of CTC detection, and its detection limit is as low as 1 CTC / well At the same time, the detection strategy has excellent detection specificity and practicability Based on the detection strategy, the research team analyzed the blood CTC level of breast cancer patients with different clinical stages, and achieved 93.9% of the positive detection rate of cancer (14 / 15), and found that the CTC detection level was closely related to the clinical stage of breast cancer patients This work provides a new idea for the study of direct detection of CTC in the whole blood, and is of great significance for the early diagnosis and prognosis monitoring of tumor patients Recently, relevant achievements have been published online in the top journal of chemistry, German Applied Chemistry (angel Chem Int ed 2019, DOI: 10.1002 / anie 201907605) Guo Hanhan, a joint student of the Institute of physical architecture / Fujian agricultural and Forestry University, is the first author of the paper, and Chen Zhuo, Chen Xueyuan and song Xiaorong, Ph.D., are the corresponding authors This work cooperates with the team of Dr Lei Wen of breast cancer surgery and Dr He Cheng of Pathology Department of Fujian cancer hospital in patient sample collection and CTC commercial tumor cell size separation (Iset) detection Fig 1, a) electron microscopic characterization of nano-sized naeuf4; b) emission spectrum of nano-sized particles in phosphate buffer and reinforcement solution and photo of light emission under ultraviolet lamp irradiation; c) Flow cytometry before and after the combination of MCF-7 breast cancer cells and nano probes; d) linear relationship between time-resolved fluorescence signal and CTC concentration; E) box type statistical analysis chart of blood CTC in patients with different stages of breast cancer; F) comparison of CTC level detected by rare earth nano probes and commercial Iset (source: angel Chem Int ed.) previously, Chen Zhuo's team and Chen Xueyuan's team have made a series of important progress in biomedical application research based on rare earth upconversion luminescent nanomaterials For example, they have developed an in vitro detection platform for tumor markers based on Upconversion luminescent nanoprobes (nanoscale 2015, 7, 4274-4290; cover article) and application of photodynamic therapy (nanoscale 2018, 33, 15485-15495; inner cover article)