Self-propelled quantum dots-based spherical nucleic amplifier for ratiometric imaging of intracellular microRNAs

Real-time in-situ visualization and sensitive detection of thimbleful tumor-related microRNAs (miRNAs) in living cells is still unmet. Especially, poor amplification efficiency and resistance against complex intracellular envi-ronment hinder amplifiers' widespread applications in vivo . Herein, we report enzyme-free self-propelled quantum dots-based spherical nucleic acids (QDs-based SNAs, also named TSD-QDs) as a ratiometric amplifier for stable, efficient, and sensitive detection and imaging of miRNAs in biological samples and living cells. The ratiometric amplifier is proved possesses outstanding stability in human serum and cells, as well as prominent recognition capability for miRNAs. More importantly, the ingeniously designed tail sequence of fuel strand (FS) could lead to high operating efficiency and excellent detection performance of TSD-QDs for non-enzyme detection in vitro (in the range of 10 fM-150 nM with a limit of detection (LOD) of 5.8 fM). Furthermore, the spherical nucleic acids (SNAs) structure can endow TSD-QDs with favorable photostability and high resistance against to the nuclease, thus benefit its applications in intracellular miRNA-21 monitoring via fluorescence imaging. With these advantages, the proposed TSD-QDs based amplifier enables accurate and effective moni-toring of the miRNAs expression levels in living cells (A549, normal QSG-7701, Hela and MCF-7 cells), and poses great potential in medical diagnostics and biomedical applications.

Automated summary

This study presents a ratiometric amplifier based on quantum dots and spherical nucleic acids for accurate, efficient, and sensitive detection and imaging of miRNAs inside living cells, showing stability and recognition capability. The amplifier demonstrates high efficiency and excellent detection performance in vitro.