Size-selected DNA hydrogels-based sensor with efficient intracellular delivery for imaging mRNA

Efficient delivery of DNA-based single-component hydrogels (DNA hydrogels) into cell is current challenge for its application in cell imaging. Since the size of nanomaterials affects its intracellular delivery, to identify an optimal size of DNA hydrogels, we designed a series of DNA sequences to construct three four-armed DNA structural unit including unit15, unit12 and unit9 in which the diameter of the structural unit of unit15, unit12 and unit9 were respectively estimated to be 10.2, 8.2 and 6.1 nm. These three four-armed DNA structural unit was assembled into three size-controlled DNA hydrogels (named DNA hydrogels15, DNA hydrogels12 and DNA hydrogels9, respectively) by DNA linker. These three DNA hydrogels could split by target c-myc mRNA and were tested in buffer. The response times of DNA hydrogels15, DNA hydrogels12 and DNA hydrogels9 to c-myc mRNA were 40 min, 30mins and 20 min, respectively, and their limits of detection were calculated to be 48.5 pM, 67.6 pM and 90.0 pM, respectively. Fluorescence imaging using these three DNA hydrogels indicated that DNA hydrogels12 internalized by the cells taken up ∼2 times higher than that of DNA hydrogels15. Taking the vitro detection and efficient delivery together, DNA hydrogels12 could be the optimal size, which provide an interesting insight into the DNA hydrogels-based biosensor.