Shell penetration/free energy-driven crosstalk between intelligent DNA nanomachines for ultrasensitive detection of circulating tumor cells. (April 2023)

• Record Type: Journal Article
• Authors: Wu, Jingting; Liu, Ran; Zheng, Xiaoqi; Chen, Linhuan; Wu, Zai-Sheng
• Is Part Of: Nano today. Volume 49(2023)
• Publication Date: 2023-04
• Subjects: DNA nanomachine -- Toehold-hidden core/shell nanostructure -- Stimuli-responsive key homing -- Shell penetration/free energy-driven autonomous circuit -- Circulating tumor cells (CTCs); Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2023.101808
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: Because of the extraordinary rarity, CTC detection remains a technological challenge. In this contribution, a stimuli-responsive intelligent DNA nanomachine system is demonstrated for ultrasensitive and specific CTC detection via a shell penetration/free energy-driven autonomous circuit. The responsive toeholds designed in linear probes are shielded by protective DNA self-assembled outer shell and hidden inwards from the attack of fuel strands, proposing an innovative concept different from conventional DNA hairpin-based catalytic reactions. DNA machines are very stable in the 'OFF' state, almost completely suppressing the background fluorescence. A linear trigger can permeate through outer shell and ignite the inner responsive toeholds, achieving an amplification fluorescent signal. CTC is specifically screened in a linear response range of three orders of magnitude with a detection limit of 2 cells/200 μL with almost 100% accuracy, indicating 3.4～50-fold improvement in assay ability. Graphical Abstract: ga1 Highlights: Intelligent DNA nanomachines for ultrasensitive CTC detection via shell penetration/free energy-driven autonomous circuit. Shell prevents toehold sites from binding to surface-confined fuels but allows reconfigurable fuels to enter the interior. Nanomachine is only activated in the 'ON' state, substantially improving the signal-to-noise ratio. Combination with tumor cell-recognizing aptamer, the ability of TRDN system to screen CTC is improved by 3.4～50-fold.