Trojan Horse Delivery of Spherical Nucleic Acid Probes into the Cytoplasm for High-Fidelity Imaging of MicroRNAs.

We report a Trojan horse strategy to efficiently deliver the spherical nucleic acid probes (namely, nanoflares) into the cytoplasm for microRNA (miRNA) imaging with high fidelity, breaking through the cytoplasmic transport dilemma of RNA probes in living cells. The nanoflare is encapsulated into a "Trojan horse" consisting of zwitterionic choline phosphates (CPs) and acid-degradable crosslinkers; the former effectively promotes cell uptake and the latter triggers instantaneous liberation of the nanoflare probes from the lysosome to the cytoplasm. The exposed nanoflares in the cytoplasm can be lightened up by the target miRNAs specifically. Compared with the conventional nanoflares as well as the improved ones in previous reports, the "Trojan horse" nanoflares avoid nuclease degradation and thiol displacement during the delivery process, providing unprecedentedly high accuracy for intracellular miRNA imaging.