In Situ Hand-in-Hand DNA Tile Assembly: A pH-Driven and Aptamer-Targeted DNA Nanostructure for TK1 mRNA Visualization and Synergetic Killing of Cancer Cells

In situ stimuli-responsive molecular devices have gained much attention in biomedical areas due to their characteristics of increased image contrast and drug accumulation. Herein, we present a hand-in-hand in situ tile assembly for improved visualization of TK1 mRNA and killing of cancer cells. A pH-responsive and aptamer-functionalized tile motif (pH-Apt-TM) was first formed by four single-strand DNA, possessing pH-responsiveness and intracellular TK1 mRNA recognition capacity. When encountering target cells, the pH-Apt-TM could recognize target receptors on the cell surface through the aptamer domain. Meanwhile, the extracellular acidic pH gathered the pH-Apt-TM into a multifunctional hand-in-hand DNA tile assembly (HDTA) on the cells' surface. Compared to the pH-Apt-TM, studies revealed that the HDTA exhibited enhanced recognition, efficient cellular uptake, and improved visualization of TK1 mRNA, accompanied by gene silencing. Moreover, using Dox as a chemotherapeutic model, specific drug delivery and enhanced cell killing were achieved with target cells.