Modular DNA-Origami-Based Nanoarrays Enhance Cell Binding Affinity through the “Lock-and-Key” Interaction

Surface
proteins of cells are generally recognized through receptor–ligand
interactions (RLIs) in disease diagnosis, but their nonuniform spatial
distribution and higher-order structure lead to low binding affinity.
Constructing nanotopologies that match the spatial distribution of
membrane proteins to improve the binding affinity remains a challenge.
Inspired by the multiantigen recognition of immune synapses, we developed
modular DNA-origami-based nanoarrays with multivalent aptamers. By
adjusting the valency and interspacing of the aptamers, we constructed
specific nanotopology to match the spatial distribution of target
protein clusters and avoid potential steric hindrance. We found that
the nanoarrays significantly enhanced the binding affinity of target
cells and synergistically recognized low-affinity antigen-specific
cells. In addition, DNA nanoarrays used for the clinical detection
of circulating tumor cells successfully verified their precise recognition
ability and high-affinity RLIs. Such nanoarrays will further promote
the potential application of DNA materials in clinical detection and
even cell membrane engineering.