Intramolecular entropy-driven amplifier assembled on a DNA octahedron enables rapid imaging of dual cancer-related long noncoding RNAs.

Long noncoding RNAs (lncRNAs) are a category of pivotal transcriptional regulators, and their dysregulation is correlated with various cancers. The reaction rate of traditional entropy-driven catalysis (EDC) relies on the diffusion of free reactants, resulting in slow reaction kinetics. Herein, we engineer an intramolecular entropy-driven amplifier assembled on a DNA octahedron for rapid imaging of dual cancer-related lncRNAs. In this amplifier, the DNA octahedron strategically incorporates six different functional modules on each of its six vertices. The six functional modules can be divided into three groups, including two binding modules for tumor cell capture, two recognition modules for lncRNA identification, and two amplification modules for fuel-strand-driven signal amplification. The engineering of the DNA octahedron not only integrates all functional modules into a single molecular scaffold, but also provides abundant sites for the simultaneous detection of dual cancer-related lncRNAs. This integration can effectively accelerate the reaction kinetics due to the spatial confinement effect of the DNA octahedron. The assay can be completed within 80 min, and achieves limits of detection (LOD) of 0.66 fM for the MALAT1 assay and 0.93 fM for the HOTAIR assay. Moreover, it enables not only single-cell quantification and accurate discrimination of MALAT1 and HOTAIR in cancerous and normal breast tissues, but also rapid imaging of dual lncRNAs in living cells. This proof-of-concept work shows promising potential in clinical diagnostics and postoperative monitoring.