Accurate and sensitive identification of cancer cells is of great importance for cancer diagnosis and prognosis. DNA circuits with high sensitivity have promise for detecting tumor-associated molecules, yet are constrained with limited tumor specificity due to the "on target, off cancer" effect. To address this issue, we propose a multi-pathway integrated DNA logic circuit (MDLC) system by integrating two AND-gate circuit modules for the highly specific and sensitive identification of cancer cells. Upon delivery into cancer cells, the MDLC system is synergistically activated by the three distinct tumor-specific biomarkers (O6-methylguanine-DNA methyltransferase, Apurinic/apyrimidinic endonuclease 1, and microRNA-21), thereby triggering a cascaded DNA circuit to generate amplified fluorescence signals. The MDLC system promises high specificity and broad applicability, which enables effective identification of three positive cancer cells (MCF-7, HepG2, and MDA-MB-231) from normal cells (MCF-10A). Further in vivo studies demonstrate the ability of this system to precisely recognize cancer cells and therefore excels in tumor imaging. Collectively, this work illustrates a simple and powerful strategy for developing DNA logic circuits, bringing new avenues for precise cancer diagnosis and biomedical applications.
Keywords: DNA logic circuit; cancer identification; cascade DNA reaction; tumor biomarkers.
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