Guo, Linjie; Zhang, Yueyue; Wang, Yue; Xie, Mo; Dai, Jiangbing; Qu, Zhibei; Zhou, Mo; Cao, Shuting; Shi, Jiye; Wang, Lihua; Zuo, Xiaolei; Fan, Chunhai; Li, Jiang

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

2022, 61, 1433-7851

Guo, Linjie; Zhang, Yueyue; Wang, Yue; Xie, Mo; Dai, Jiangbing; Qu, Zhibei; Zhou, Mo; Cao, Shuting; Shi, Jiye; Wang, Lihua; Zuo, Xiaolei; Fan, Chunhai; Li, Jiang

Multivalent interactions of biomolecules play pivotal roles in physiological and pathological settings. Whereas the directionality of the interactions is crucial, the state-of-the-art synthetic multivalent ligand-receptor systems generally lack programmable approaches for orthogonal directionality. Here, we report the design of programmable atom-like nanoparticles (aptPANs) to direct multivalent aptamer-receptor binding on the cell interface. The positions of the aptamer motifs can be prescribed on tetrahedral DNA frameworks to realize atom-like orthogonal valence and direction, enabling the construction of multivalent molecules with fixed aptamer copy numbers but different directionality. These directional-yet-flexible aptPAN molecules exhibit the adaptability to the receptor distribution on cell surfaces. We demonstrate the high-affinity tumor cell binding with a linear aptPAN oligomer (approximate to 13-fold improved compared to free aptamers), which leads to approximate to 50 % suppression of cell growth.