Size‐Independent Transmembrane Transporting of Single Tetrahedral DNA Nanostructures

Abstract

DNA nanostructures have attracted considerable attention as drug delivery carriers. However, the transmembrane kinetics of DNA nanostructures remains less explored. Herein, the dynamic process of transporting single tetrahedral DNA nanostructures (TDNs) is monitored in real time using a force‐tracing technique based on atomic force microscopy. The results show that transporting single TDNs into living HeLa cells need ≈53 pN force and ≈25 ms duration with the average speed of ≈0.6 µm s−1. Interestingly, the dynamic parameters are irrelevant to the size of TDNs, while the larger TDNs rotated slightly during the transporting process. Meanwhile, both the results from single‐molecule force tracing and ensemble fluorescence imaging demonstrate that the different size TDNs transmembrane transporting depends on caveolin‐mediated endocytosis.

Biological Effect of Differently Sized Tetrahedral Framework Nucleic Acids: Endocytosis, Proliferation, Migration, and Biodistribution

“…It was evident that all of the TFNAs could promote the proliferation of ASCs compared with the control after treatment for 24 h (Figure a). This was consistent with our previous studies. ,, Notably, T21 exhibited the strongest effect in promoting ASCs proliferation compared with the other five TFNAs. Furthermore, the cell cycle was assessed by FCM to examine TFNAs that enhance the proliferation of ASCs (Figure b,c).…”

“…These TFNAs were denoted as TFNAs-7 (T7), TFNAs-13 (T13), TFNAs-17 (T17), TFNAs-21 (T21), TFNAs-26 (T26), and TFNAs-37 (T37) and contain 7, 13, 17, 21, 26, and 37 bp, respectively. The sizes of these three-dimensional (3D) DNA nanostructures were estimated using the edge length based on the distance between each base pair (bps are 0.34 nm in a double helix), as previously reported . Therefore, the lengths of the edges for T7, T13, T17, T21, T26, and T37 were 2.4, 4.4, 5.8, 7.1, 8.8, and 12.6 nm, respectively (Figure a).…”

“…Several reports have suggested that well-defined 3D TFNAs of different sizes are transported into mammalian cells, which are dependent on the caveolin-mediated endocytosis pathway, and then accumulate in lysosomes. Additional studies have indicated that the transporting force and average speed of differently sized TFNAs are size-independent. − Therefore, our study aimed to illustrate the cell response to differently sized TFNAs, and the penetrative ability of TFNAs of different sizes into adipose stem cells (ASCs) and the biodistribution of differently sized TFNAs in mouse. Six types of TFNAs with different sizes were tested, including TFNAs-7 (T7), TFNAs-13 (T13), TFNAs-17 (T17), TFNAs-21 (T21), TFNAs-26 (T26), and TFNAs-37 (T37), each of which contain 7, 13, 17, 21, 26, and 37 base pairs (bp), respectively.…”

Application of Programmable Tetrahedral Framework Nucleic Acid-Based Nanomaterials in Neurological Disorders: Progress and Prospects

“…And also, he found that the tFNAs with different size exhibited different rotation angles in the final stage. Besides that, Chen found that the transportation of tFNA in transmembrane was depended on caveolin-mediated endocytosis, which was consistent with Liang's report (Chen et al, 2020). Fan also expanded its application.…”

“…For instance, Tian. et al added AS1411 to one of the four strands and synthesized an aptamer-modified tFNA (Apt-tFNA) (Tian et al, 2020). Then, under hypoxia, they contrasted intracellular localizations of AS1411-modified tFNA with those of unmodified tFNA in various cells.…”