Multilevel dual-cyclic DNA cascade amplification strategy for cancer cell inhibition and ultrasensitive electrochemical detection.

Authors

Wenwen Xu, Yalong Qiao, Qiuting Wang, Lei Feng, Pinghua Ling

Published in

Analytica chimica acta. Volume 1425. Pages 346247. Dec 01, 2026. Epub Sep 09, 2026.

Abstract

Integrating ultrasensitive biosensing with cellular behavior regulation is crucial for cancer theranostics, yet traditional methods lack sensitivity and spatial precision. Programmable DNA nanodevices enabling simultaneous receptor modulation and signal amplification provide a promising paradigm to address these challenges. Herein, an electrochemical biosensor based on a multilevel dual-cyclic DNA cascade amplification strategy was developed for cancer cell detection and cellular behavior regulation.
The cell-surface DNA nanodevice comprises aptamers A1 and A2, which specifically recognize MET and CD71 proteins on cancer cell membranes, respectively. In the presence of an initiator strand S1, a cascaded hairpin-mediated strand displacement reaction is triggered on the cell surface, bringing MET and CD71 into close proximity. The spatial restriction blocks the hepatocyte growth factor (HGF)-MET interaction, inhibiting cell migration. Concurrently, the reaction releases H3H4 duplexes into the culture medium. Upon the introduction of hairpin probes functionalized with bimetallic platinum-palladium nanoparticles (PtPd/H6), H3H4 duplexes initiate a secondary strand displacement cycle on the electrode surface. This electrode-confined cascade recruits an amount of PtPd/H6, which exhibits excellent electrocatalytic activity toward H₂O₂ reduction to amplify the electrochemical signal. The biosensor displays a linear response to cell concentrations ranging from 10² to 5 × 10⁶ cells/mL, with a limit of detection of 4 cells/mL.
The dual functional sensing strategy provides a reliable approach for integrated cellular regulation and electrochemical analysis.

PMID:
42951508
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.

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