Non-invasive isolation of rare circulating tumor cells with a DNA mimic of double-sided tape using multimeric aptamers

Chen, Yongli; Wang, Wei; Tyagi, Deependra; Carrier, Andrew; Cui, Shufen; He, Shengnan; Zhang, Xu

doi:10.1039/c9nr00364a

Cited by 25 publications

(19 citation statements)

References 29 publications

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“…The long multivalent DNA strands containing multiple repeated aptamer sequences are synthesized in situ by electrode-immobilized DNA primer/circular template complexes via RCA. The RCA-generated strands, which can reach out to a depth of tens of micrometers into the cell suspension and enable sufficient contact with the cells, − can specifically bind the MCF-7 target cells through the interaction between the aptamer segments and the epithelial cell adhesion molecules (EpCAMs) on MCF-7 cells . Moreover, the repeated target-binding aptamer segments can bind MCF-7 cells in a cooperative fashion by the multivalent binding probes, which significantly enhance the avidity to the target cells. − After the CTCs are captured on the electrode, anti-EpCAM antibodies and horseradish peroxidase coconjugated gold nanoparticle (anti-EpCAM/HRP-AuNP) signal probes can attach to the captured cells to trigger the enzyme catalytic reaction, which generates amplified current responses for the sensitive detection of CTCs.…”

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confidence: 99%

In Situ-Generated Multivalent Aptamer Network for Efficient Capture and Sensitive Electrochemical Detection of Circulating Tumor Cells in Whole Blood

Yang

Jiang

et al. 2020

Anal. Chem.

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Monitoring circulating tumor cells (CTCs) in human blood can offer useful information for convenient metastasis diagnosis, prognosis, and treatment of cancers. However, it remains a substantial challenge to detect CTCs because of their particular scarcity in complex peripheral blood. Herein, we describe an in situ-generated multivalent aptamer network-modified electrode interface for efficiently capturing and sensitively detecting CTCs in whole blood by electrochemistry. Such an interface was fabricated via rolling circle amplification extension of the electrode-immobilized primer/circular DNA complexes for the yield of long ssDNA strands with many repeated aptamer segments, which could achieve efficient capture of rare CTCs in a multivalent cooperative manner. The antibody and horseradish peroxidase-functionalized gold nanoparticles further specifically associated with the surface-bound CTCs and generated electrocatalytically amplified current outputs for highly sensitive detection of CTCs with an attractive detection limit of five cells. Also, the multivalent aptamer network interface could successfully distinguish the target cells from other control cells and achieve CTC detection in whole blood, demonstrating its promising potential for monitoring different rare CTCs in human blood.

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confidence: 99%

In Situ-Generated Multivalent Aptamer Network for Efficient Capture and Sensitive Electrochemical Detection of Circulating Tumor Cells in Whole Blood

Yang

Jiang

et al. 2020

Anal. Chem.

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“…In particular, multivalent aptamers allow elevated local concentrations of aptamers and increased binding avidities between the capturing motif and the target. As a result, the multivalent strategy has been widely used in many large-sized target detections, such as human cells [ 6 , 18 , 42 , 67 , 99 ] and bacterial cells [ 87 , 100 , 101 , 102 ] in whole-cell assays. In addition, the multivalent strategy has also been used to detect smaller sized targets, such as extracellular vehicles [ 54 , 103 ] and small molecules [ 104 ].…”

Section: Biosensing and Biomedical Applicationsmentioning

confidence: 99%

Multivalent Aptamer Approach: Designs, Strategies, and Applications

et al. 2022

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Aptamers are short and single-stranded DNA or RNA molecules with highly programmable structures that give them the ability to interact specifically with a large variety of targets, including proteins, cells, and small molecules. Multivalent aptamers refer to molecular constructs that combine two or more identical or different types of aptamers. Multivalency increases the avidity of aptamers, a particularly advantageous feature that allows for significantly increased binding affinities in comparison with aptamer monomers. Another advantage of multivalency is increased aptamer stabilities that confer improved performances under physiological conditions for various applications in clinical settings. The current study aims to review the most recent developments in multivalent aptamer research. The review will first discuss structures of multivalent aptamers. This is followed by detailed discussions on design strategies of multivalent aptamer approaches. Finally, recent developments of the multivalent aptamer approach in biosensing and biomedical applications are highlighted.

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Section: Aptamer-based Isolation Release and Analysis Of Ctcsmentioning

confidence: 99%

Aptamer-Based Liquid Biopsy

Wang

Zhu

et al. 2020

ACS Appl. Bio Mater.

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Liquid biopsy allows noninvasive and real-time analysis of tumor-derived circulating targets in body fluids, holding great value for cancer diagnosis, prognosis, personalized therapy, as well as the understanding of mechanisms underlying tumorigenesis and progression. However, the low concentration and heterogeneity of circulating targets and the complexity of body fluids bring daunting technical challenges to liquid biopsy. Aptamers with many unique properties are considered as promising recognition ligands for liquid biopsy. Their facile modification and affinity regulation afford numerous platforms for efficient isolation and release of circulating targets. With versatile structural design and engineering, aptamers also offer many strategies for sensitive detection and analysis of circulating targets. In this review, recent progress in aptamer-based liquid biopsy is summarized, with a focus on the isolation and detection of circulating tumor cells (CTCs) and extracellular vesicles (EVs). First, recently emerged strategies for evolving aptamers against circulating targets are introduced, and existing aptamers successfully applied in the liquid biopsy are comprehensively summarized, including their targets, sequences, affinities, etc. Then, aptamer-based approaches for CTC isolation, release, and analysis are summarized. Additionally, aptamer-mediated signal transduction and amplification for the detection of EVs are also reviewed. Finally, the challenges and future perspectives in this field are discussed.

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Non-invasive isolation of rare circulating tumor cells with a DNA mimic of double-sided tape using multimeric aptamers

Abstract: An efficient, selective, and non-invasive double-sided tape (DST) DNA device was developed to isolate rare circulating tumor cells from whole blood.

Cited by 25 publications

References 29 publications

In Situ-Generated Multivalent Aptamer Network for Efficient Capture and Sensitive Electrochemical Detection of Circulating Tumor Cells in Whole Blood

In Situ-Generated Multivalent Aptamer Network for Efficient Capture and Sensitive Electrochemical Detection of Circulating Tumor Cells in Whole Blood

Multivalent Aptamer Approach: Designs, Strategies, and Applications

Aptamer-Based Liquid Biopsy

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