Poly‐Adenine‐Based Spherical Nucleic Acids for Efficient Live‐Cell MicroRNA Capture

Abstract Direct delivery of exogenous non‐coding nucleic acids into living cells has attracted intense interest in biological applications. However, the cell entry efficiency and target capture ability remain to be improved. Herein, we report a method for compartmenting the nucleic acids on the surface of poly‐adenine‐based spherical nucleic acids (polyA‐SNAs) for efficient capture of oncogenic microRNAs (miRNAs) in living cells. We find that polyA‐SNAs exhibit high cell entry efficiency, which is insensitive to the configuration of the anti‐miRNA sequences. By programming the length of polyAs, we precisely engineered the spatial configuration of the anti‐miRNA sequences in polyA‐SNAs. Compartmentalized polyA‐SNAs bind to miRNAs with improved capture ability as compared to densely compacted SNAs. We further demonstrate that polyA‐SNAs serve as high‐efficacy miRNA sponges for capturing oncogenic miRNAs both in living cells and in mice. The efficient inhibition of miRNAs results in significant suppression of tumor growth.