DNA logic gate for cancer cells identification, detection, and modulation of cell–cell interactions

• Published in: Microchemical journal 2024-12, Vol.207, p.111840, Article 111840
• Main Authors: Ling, Pinghua, Xu, Wenwen, Qiao, Yalong, Song, Danjie, Tang, Chuanye, Wang, Linyu, Yang, Pei
• Format: Article
• Language: English
• Subjects: Cell–cell interactions; DNA logic-gate; Electrochemical sensor; Modulation
• ISSN: 0026-265X
• DOI: 10.1016/j.microc.2024.111840

An “AND” logic-gated DNA strategy that incorporates membrane protein and an extracellular acid responsive split i-motif was designed for the precise detection of cancer cells and modulation of the interaction between T cells and cancer cells. [Display omitted] •A logic-gated DNA molecular machine was designed for cell–cell interactions.•The logic-gated DNA molecular machine contained a membrane protein aptamer and an extracellular acid responsive split i-motif.•Benefiting from the DNA logic gate and catalytic hairpin assembly, this strategy exhibited excellent precise and sensitivity.•The method could be used in complex matrix. The precise detection of cancer cells and modulation of cell–cell interactions would be highly desired for noninvasive and nontoxic cancer treatments but it remains challenging due to the existence of biomarkers on both normal and tumor cells. In this work, we engineered a logic-gated DNA molecular machine incorporating a membrane protein aptamer and an extracellular acid responsive split i-motif for the precise identification and detection of cancer cells, as well as the mediation of cell–cell interactions. In this system, only in the presence of both the membrane protein and protons, the logic-gated DNA molecular machine is activated to perform the “AND” logic operation to induce catalytic hairpin assembly (CHA) on the electrode, leading to the formation of G-quadruplex/hemin and the generation of an amplified electrochemical signal. On the other hand, the formed “AND” logic could hybridize with the DNA fragment on T-cell, effectively shorting the distance between T-cell and cancer cells. Benefiting from the DNA logic gate and CHA, this strategy could not only precisely identify cancer cells, but also show a sensitive analysis of cancer cells with a detection limit of 15 cells/mL. The logic-gated DNA molecular machine achieved the identification of cancer cells and modulation of intercellular interactions, providing a new idea for precise disease diagnosis and therapy.