Bioinspired DNA Nanointerface with Anisotropic Aptamers for Accurate Capture of Circulating Tumor Cells

Abstract

The capture and analysis of circulating tumor cells (CTCs) have provided a non-invasive entry for cancer diagnosis and disease monitoring. Despite recent development in affinity-based CTCs isolation, it remains challenging to achieve efficient capture toward CTCs with dynamic surface expression. Enlightened by the synergistic effect insideimmune synapses, the development of a nanointerface engineered with topology-defined anisotropic aptamers programmed by DNA scaffold (DNA nanosynapse), for accurate CTCs isolation, is herein reported. As compared to isotropic aptamers, the DNA nanosynapse exhibits enhanced anchoring on the cell membrane with both high and low epithelial cell adhesion molecule (EpCAM) expression. This nanointerface enables accurate capture toward CTCs of heterogeneous EpCAM, without dramatically proportional change inside the mixture of diverse phenotypes. By applying this nanoplatform, CTCs detection as well as downstream analysis for measuring disease status can be achieved in clinical samples from breast cancer patients.

Multivalent Aptamer Approach: Designs, Strategies, and Applications

“…Traditionally, CTC detections face issues such as low CTC occurrences in clinical samples and difficulties in targeting appropriate CTC biomarkers, since the presence of these surface markers is known to be non-uniform between individual patients [ 18 ]. To overcome these obstacles, one can target different arrays of CTC biomarkers simultaneously to both increase binding avidities and prevent the off-target effects due to the reduced or loss of certain surface biomarker expressions on the CTCs [ 88 ]. For example, Lin et al [ 18 ] developed a dual-aptamer-tethered network system that allowed DNA-triggered reversible isolation-and-release of CTCs by tethering Sgc8c and Sgc4f aptamers onto a ssDNA scaffold.…”

DNA nanostructure-based nucleic acid probes: construction and biological applications

“…In this way, cell sorting from a cell mixture was achieved with minimum cell damage. Enlightened by the synergistic effect adapted by the immune system, Li and Zhang's group 132 developed a bioinspired DNA nanointerface (named as DNA nanosynapse) by coupling three different aptamers to the three vertices of the DNA tetrahedron. Via the simultaneous binding of the three aptamers to their respective target proteins on the CTC surface, the DNA nanosynapse can persistently adhere to the membrane of CTCs, thus showing strong resistance toward endocytosis and making it a promising tool for CTC capture, detection and downstream disease status analysis.…”

Recent trends in sorbents for bioaffinity chromatography

“…Anti‐platelet adhesion and in situ capture of circulating endothelial progenitor cells on polytetrafluoroethylene (PTFE) surface modified with poly(2‐methacryloyloxyethyl phosphorylcholine) and hemocompatible peptide 1 (HCP‐1) were investigated by Liu et al [149]. Bioinspired DNA nanointerface with anisotropic aptamers was evaluated for accurate capture of circulating tumor cells [150]. A natural biointerface based on cancer cell membranes was used for a specific capture and release of circulating tumor cells [151].…”