Fluorinated molecular beacons as functional DNA nanomolecules for cellular imaging

Molecular beacons (MBs) are simple, but practical, fluorescent nanoprobes widely used to detect small molecules, nucleic acids and proteins. However, some challenges still remain when MBs are employed in complex biological environments, such as instability and non-target interference. To meet such challenges, we have designed and synthesized fluorinated molecular beacons (FMBs) as functional DNA nanomolecules for cellular imaging, in which the stem sequence is simply composed of artificial nucleotides with 3,5-bis(trifluoromethyl)benzene (F) as the surrogate base of natural A, T, C and G bases. The introduction of F base into MBs significantly increases their hydrophobicity, and the stem is formed by the assembly of self-complementary base F nucleotides through hydrophobic interactions. Fluorescence studies revealed that FMBs confer improved stability over conventional MBs. To demonstrate the application of FMBs for cellular imaging, we constructed an FMB to detect mRNA in MCF-7 cells, and the FMB was proven to be a practical nanoprobe for cellular imaging of mRNA.