Target-triggered hairpin-free chain-branching growth of DNA dendrimers for contrast-enhanced imaging in living cells by avoiding signal dispersion

Abstract

The development of amplification strategies is one of the central challenges for detection of low-abundance targets. One-to-many (1:M) amplification strategies in which one target lights many signal probes, has improved the detection sensitivity in bulk solution, but with discounted contrast in cell imaging, because the lighted probes are dissociative and dispersible. In this work, a one-to-large (1:L) signaling mechanism, in which the lighted probes were orderly connected to each other, was conceptually proposed to enhance the contrast in cell imaging by avoiding signal dispersion in amplification. Accordingly, target-triggered hairpin-free chain-branching assembly (HFCBA) holds great potential to implement the 1:L mechanism, but using it in cell imaging has yet to be demonstrated. As a proof of concept, a group of probes were first programmed to implement miRNA-21-triggered HFCBA. After transfection of probes, gradually-growing signal flares in cells were monitored along with the growth of DNA dendrimers; and the in situ fluorescence accumulation in HFCBA resulted in highly-enhanced contrast to the surrounding by avoiding signal dispersion in amplification. The contrast-enhanced imaging with signal amplification is significant for biological analysis and molecular medicine. We expect the 1:L mechanism will provide a new thought for high-performance imaging of biomarkers in cells.