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
posted on 2021-07-20, 15:14authored byWenjie Ma, Biao Chen, Ruichen Jia, Huanhuan Sun, Jin Huang, Hong Cheng, Huizhen Wang, Xiaoxiao He, Kemin Wang
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.