American Chemical Society
ja2c13825_si_001.pdf (13.4 MB)

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

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journal contribution
posted on 2023-02-22, 21:13 authored by Miao Mao, Zhun Lin, Liang Chen, Zhengyu Zou, Jie Zhang, Quanhao Dou, Jiacheng Wu, Jinglin Chen, Minhao Wu, Li Niu, Chunhai Fan, Yuanqing Zhang
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.