Indole-based Cyanine as a Nuclear RNA-Selective Two-Photon Fluorescent Probe for Live Cell Imaging

Abstract

We have demonstrated that the subcellular targeting properties of the indole-based cyanines can be tuned by the functional substituent attached onto the indole moiety in which the first example of a highly RNA-selective and two-photon active fluorescent light-up probe for high contrast and brightness TPEF images of rRNA in the nucleolus of live cells has been developed. It is important to find that this cyanine binds much stronger toward RNA than DNA in a buffer solution as well as selectively stains and targets to rRNA in the nucleolus. Remarkably, the TPEF brightness (Φσmax) is dramatically increased with 11-fold enhancement in the presence of rRNA, leading to the record high Φσmax of 228 GM for RNA. This probe not only shows good biocompatibility and superior photostability but also offers general applicability to various live cell lines including HeLa, HepG2, MCF-7, and KB cells and excellent counterstaining compatibility with commercially available DNA or protein trackers.

Recent Development of Chemosensors Based on Cyanine Platforms

“…Sensor 185 was a two-photon RNA selective indicator, devised on the basis of an indole−hemicyanine structure. 224 In the presence of RNA, a strong fluorescence peak at ∼540 nm was observed when the chemosensor was excited at 820 or 930 nm.…”

Discerning the Chemistry in Individual Organelles with Small‐Molecule Fluorescent Probes

“…[201a] In addition, in 2012, the Schmuck research group reported the pyrene-functionalized probe 103,w hich contained cationic oligopeptides for ds-DNArecognition (Scheme 35). [208] Thesmall size and relative hydrophilicity of the small-molecule probe enabled it to penetrate deeply into the nucleus,w hile the positive charge allows its interaction with the RNA chain. Cell imaging demonstrated that this probe could be easily taken up by cells and could visualize nuclear DNA.…”

“…By utilizing an indole-based positively charged cyanine probe (MPI (104), Scheme 36), Wong and co-workers achieved the highly selective two-photon imaging of ribosomal RNA( rRNA) in the nucleolus of live cells. [208] Thesmall size and relative hydrophilicity of the small-molecule probe enabled it to penetrate deeply into the nucleus,w hile the positive charge allows its interaction with the RNA chain. Live-cell imaging clearly indicates localization of the probe within the nucleolus ( Figure 19).…”

Recent Advances in Nanoformulated Chemotherapeutic Drug Delivery (2015‐2019)

“…Still now small molecular platinum drugs having fluorescent properties are rarely reported. Cyanine lead structures possess fluorescent enhancement properties upon enclosement in a hydrophobic environment . Cyanine derivatives on complexation with platinum afford cyanine‐platinum conjugates (CPCs) (Figure ).…”