The
reprogramming of cell signaling and behavior through
the artificial
control of cell surface receptor oligomerization shows great promise
in biomedical research and cell-based therapy. However, it remains
challenging to achieve combinatorial recognition in a complicated
environment and logical regulation of receptors for desirable cellular
behavior. Herein, we develop a logic-gated DNA nanodevice with responsiveness
to multiple environmental inputs for logically controlled assembly
of heterogeneous receptors to modulate signaling. The “AND”
gate nanodevice uses an i-motif and an ATP-binding aptamer as environmental
cue-responsive units, which can successfully implement a logic operation
to manipulate receptors on the cell surface. In the presence of both
protons and ATP, the DNA nanodevice is activated to selectively assemble
MET and CD71, which modulate the HGF/MET signaling, resulting in cytoskeletal
reorganization to inhibit cancer cell motility in a tumor-like microenvironment.
Our strategy would be highly promising for precision therapeutics,
including controlled drug release and cancer treatment
