Self-assembled DNA nanoparticles enable cascade circuits for mRNA detection and imaging in living cells

Fluorescence molecular probes have been regarded as a valuable tool for RNA detection and imaging. However, the pivotal challenge is how to develop an efficient fluorescence imaging platform for accurate identification of RNA molecules with low expression in complicated physiological environments. Herein, we construct the DNA nanoparticles to glutathione (GSH)-responsive controllable release of hairpin reactants for catalytic hairpin assembly (CHA)-hybridization chain reaction (HCR) cascade circuits, which enables the analysis and imaging of low-abundance target mRNA in living cells. The aptamer-tethered DNA nanoparticles are constructed via the self-assembly of single-stranded DNAs (ssDNAs), exhibiting sufficient stability, cell-specific penetration, and precise controllability. Moreover, the in-depth integration of different DNA cascade circuits shows the improved sensing performance of DNA nanoparticles in live cell analysis. Therefore, through the combination of multi-amplifiers and programmable DNA nanostructure, the developed strategy enables accurately triggered release of hairpin reactants and further achieves sensitive imaging and quantitative evaluation of survivin mRNA in carcinoma cells, which provides a potential platform to facilitate RNA fluorescence imaging applications in early clinical cancer theranostics.