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
Wenjie Ma, Biao Chen, Ruichen Jia, Huanhuan Sun, Jin Huang, Hong Cheng, Huizhen Wang, Xiaoxiao He, Kemin Wang
Abstract
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.