Ultrasensitive Fluorescence Detection and Accurate Colocalization Visualization of Dual-miRNAs in Cancer Cells Based on the Conjugated Chain Reaction of Multifunctional Pentagon DNA Nanostructures

Herein, a multifunctional pentagon DNA nanostructure (MPDN) was assembled by the hybridization of a circular DNA scaffold containing five different fragments with five diverse DNA oligonucleotides for simultaneous sensitive detection and accurate colocalization imaging of dual-miRNAs in cancer cells. Exactly, the MPDN could specifically and efficiently internalize into folate (FA) receptor-overexpressed cells via specific binding of FA and the FA receptor to distinguish cancer cells from normal cells and transform trace amounts of targets miRNA-21 and miRNA-155 into substantial FAM and Cy5-labeled DNA polymers as the signal probe to generate two remarkable fluorescence emissions, realizing simultaneously sensitive detection of dual-miRNAs. Impressively, compared with traditional small fragment DNA probes with high fluidity, the DNA copolymers with extremely low diffusivity kept it in the originally generated position to achieve the colocalization imaging of dual-miRNAs more accurately for revealing the spatial expression information of dual-miRNAs in tissues and cells. This strategy provided programmable tool to simultaneously detect and accurately colocate dual-miRNAs for understanding normal physiology and the tumor mechanism.