An integrated and renewable interface for capture, release and analysis of circulating tumor cells.

Circulating tumor cells (CTCs) have now emerged as a type of promising circulating biomarkers in liquid biopsy and can predict the occurrence and development of cancers. In this work, an integrated and renewable interface is fabricated for the capture, release and quantitative analysis of CTCs. As designed, folate receptor-positive CTCs are captured by folic acid-modified DNA probes at the interface through the receptor-ligand interaction, and are efficiently released from the interface with the aid of bleomycin-ferrous complex-regulated cleavage. Taking MCF-7 cells as the model, the functional interface demonstrates high efficiency to selectively capture the folate receptor-positive tumor cells, and the bleomycin-ferrous complex-regulated cleavage not only easily releases the captured cells with well-maintained viability and proliferation ability, but also releases silver nanoparticles that are labeled at the cell surface for highly sensitive quantification by adopting electrochemical techniques with a detection limit of 6 cells/mL. At the meanwhile, the interface is proved to be regenerated through a simple cleavage-hybridization event and reused with high stability. Therefore, our work may provide a new idea for the collection and downstream researches of circulating tumor cells in the future.

Recent Advances in Bio-Sensing Methods for the Detection of Tumor Exosomes.

Exosomes, small vesicles with the diameters of 40-160 nm, play an important role in intercellular transport and communication. Exosomes are rich in many kinds of biomolecules, and differential expression of exosomal contents directly reflects the state of the original cells. Therefore, the tumor exosomes are appearing as promising biomarkers in liquid biopsy, and highly sensitive and specific detection of tumor exosomes may provide the information for the early diagnosis, real-time monitoring and treatment of the tumors. In this review, we summarized the recent advances in the detection of tumor exosomes, mainly focusing on the use of different analytical techniques, such as optical and electrochemical methods as well as that combination with newly-emerging microfluidic techniques, thereby providing valuable information for the application in the clinical diagnosis and management of the tumors.

Stable DNA Aptamer-Metal-Organic Framework as Horseradish Peroxidase Mimic for Ultra-Sensitive Detection of Carcinoembryonic Antigen in Serum.

Carcinoembryonic antigen (CEA) is an important broad-spectrum tumor marker. For CEA detection, a novel type of metal-organic framework (MOF) was prepared by grafting CEA aptamer-incorporated DNA tetrahedral (TDN) nanostructures into PCN-222 (Fe)-based MOF (referred as CEAapt-TDN-MOF colloid nanorods). The synthesized CEAapt-TDN-MOF is a very stable detection system due to the vertex phosphorylated TDN structure at the interface, possessing a one-year shelf-life. Moreover, it exhibits a significant horseradish peroxidase mimicking activity due to the iron porphyrin ring, which leads to a colorimetric reaction upon binding toward antibody-captured CEA. Using this method, we successfully achieved the highly specific and ultra-sensitive detection of CEA with a limit of detection as low as 3.3 pg/mL. In addition, this method can detect and analyze the target proteins in clinical serum samples, effectively identify the difference between normal individuals and patients with colon cancer, and provide a new method for the clinical diagnosis of tumors, demonstrating a great application potential.

In Situ Programmable DNA Circuit-Promoted Electrochemical Characterization of Stemlike Phenotype in Breast Cancer.

Breast cancer is one of the most common malignant diseases among women worldwide, and the existence of breast cancer stem cells is closely associated with poor outcomes. Herein, we report an electrochemical phenotyping method to characterize the stemlike phenotype in breast cancer, offering a low-cost but robust choice other than the highly expensive and experience-dependent flow cytometry. Specially, after immune-magnetic beads-assisted enrichment, an in situ programmable DNA circuit is designed using capture probes to bring in the toeholds for DNA assembly and effector probes to accelerate the removal of background signals. The electrochemical phenotyping method could sensitively determine breast cancer stem cells in a wide linear range and exhibit desirable accuracy and reliability. The method can not only monitor the phenotypic transition of breast cancer cells and the drug-reversed effect but also determinate stemlike phenotype in the mice bearing breast cancer xenograft tumor. Overall, the electrochemical phenotyping method may provide promising technical support for precise management of breast tumors.