Abstract
ObjectivesDue to the instability of microRNAs, the applications of microRNA are currently limited. Thus, we utilized tetrahedral framework nucleic acids and a targeted microRNAs to form a stable nanocomposite to explore whether this nanocomposite can promote apoptosis of tumour cells.Materials and methodsIn our study, the survivin gene, which is expressed only in tumour cells and embryonic cells, was selected as the target gene; miRNA‐214‐3p, which can reduce the expression of survivin, was modified onto tetrahedral framework nucleic acid, thereby producing a reduction in the expression of survivin upon intracellular delivery and eventually leading to tumour cell apoptosis.ResultsBy comparing the stability of microRNAs with that of microRNA‐tetrahedral framework nucleic acid, we proved the superiority of this carrier system. The results of flow cytometry showed that after treated with this complex, the ratio of A549 cells in both late and early period of apoptosis in miRNA‐214‐3p‐tetrahedral framework nucleic acid group had doubled and the cell cycle in the G2‐M phase had declined. The decrease in the expression of anti‐apoptotic protein and the increase in the expression of pro‐apoptotic protein indicate that the ability of this complex to function in cells also makes it attractive as a new targeted therapy for cancer.ConclusionThe unique expression of survivin in tumour cells and embryonic cells makes microRNA‐tetrahedral framework nucleic acid a new targeted therapy. In addition, due to the functional diversity of microRNAs, this delivery system approach can be applied to a wide variety of fields, such as targeted therapy and tissue regeneration.
Highlights
DNA nanotechnology has developed rapidly in the past 30 years.[1]
In previous studies from our group, we incubated tet‐ rahedral framework nucleic acids (tFNAs) with chemotherapeutic drugs or modified tFNAs with adapters, using the permeability of tFNAs to pene‐ trate the cell membrane into cells
We tested each group of cells and found that after 72 hours, and the ratio of A549 cells in both late and early period of apoptosis in tFNAs‐miR‐ 214‐3p group had doubled (Figure 5A)
Summary
DNA nanotechnology has developed rapidly in the past 30 years.[1]. Owing to the relative ease with which DNA can be edited, scholars have used DNA to assemble nanomaterials with different spatial structures and morphologies.[2-7]. In previous studies from our group, we incubated tFNAs with chemotherapeutic drugs or modified tFNAs with adapters, using the permeability of tFNAs to pene‐ trate the cell membrane into cells These conclusions indicate that tFNAs have great potential in the field of drug delivery.[16,19]. We linked tFNAs to miRNAs, allowing tFNAs to serve as vectors for miRNAs and utilizing the uptake potential of tFNAs to carry miRNAs into cells The use of this delivery method can overcome the instability of miRNAs, thereby increasing their intracellular efficiency. This is the first time that miRNAs have been bound to tFNAs to produce a therapeutic effect.[12]. We validated the stability of tFNAs‐miR‐214‐3p in a variety of enzymatic environ‐ ments by assaying serum stability
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