Light‐Harvesting Fluorescent Spherical Nucleic Acids Self‐Assembled from a DNA‐Grafted Conjugated Polymer for Amplified Detection of Nucleic Acids

Abstract The ultralow concentration of nucleic acids in complex biological samples requires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π‐conjugated polymers (FCPs) as a light‐harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA‐grafted FCPs are synthesized and self‐assemble into FCP‐SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light‐harvesting capability of the FCP‐SNAs. We observe that more efficient signal amplification occurs in larger FCP‐SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP‐SNA shows an antenna effect of up to 37‐fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP‐SNA is applied to amplified in situ nucleic acid detecting and imaging at the single‐cell level.