Detection of miRNA in Live Cells by Using Templated RuII‐Catalyzed Unmasking of a Fluorophore

Reactions templated by cellular nucleic acids are attractive for nucleic acid sensing or responsive systems. Herein we report the use of a photocatalyzed reductive cleavage of an immolative linker to unmask a rhodamine fluorophore, and its application to miRNA imaging. The reaction was found to proceed with a very high turnover (>4000) and provided reliable detection down to 5 pM of template by using γ-serine-modified peptide nucleic acid (PNA) probes. The reaction was used for the selective detection of miR-21 in BT474 cells and miR-31 in HeLa cells following irradiation for 30 min. The probes were introduced by using reversible permeation with streptolysin-O (SLO) or a transfection technique.