Biodegradable MnO2 nanosheet-mediated catalytic hairpin assembly for two-color imaging of mRNAs in living cells

Messenger RNA (mRNA) plays significant functions in physically conveying and interpreting genetic information, and has been considered as specific markers for tumor burden and assesses response to treatment. Sensitively and simultaneously detect and image multiple intracellular tumor-related mRNA is of great significant in early cancer detection and disease studies. However, because of their low abundance, effective signal amplification of mRNAs in living cells remains an unresolved challenge. To solve this problem, we proposed a simple but powerful strategy based on MnO2 nanosheet-mediated catalytic hairpin assembly (CHA) for two-color monitoring of mRNAs in living cells. In virtue of the excellent recognition function and high-performance of signal enhancement, catalytic hairpin assembly offers high-sensitive signal amplification for specific mRNAs in living cells. Benefit from biodegradability of MnO2 nanosheets, they can offer good biocompatibility to the living cells. MnO2 nanosheets can absorb the designed two pairs of CHA hairpin probes, protect them from enzymatic digestion, and enable effective intracellular delivery of probes for signal amplification cascade triggered by target mRNA. This method realizes facile and sensitive mRNA imaging in living cells, and enable to effectively differentiate cancer cells from normal cells and identify the fluctuation of mRNA expression levels in living cells, providing a powerful platform for sensitive detection and simultaneous monitoring of multiple mRNAs, thus improve the reliability of identify cancer at an early stage.