DNA-Based Nanomedicine with Targeting and Enhancement of Therapeutic Efficacy of Breast Cancer Cells

Abstract

Recently, a DNA tetrahedron has been reported to be a novel nanomedicine and promising drug vector because of its compactness, biocompatibility, biosafety, and editability. Here, we modified the DNA tetrahedron with a DNA aptamer (AS1411) as a DNA-based delivery system, which could bind to nucleolin for its cancer cell selectivity. Nucleolin is a specific biomarker protein overexpressed on membranes of malignant cancer cells and its deregulation is implicated in cell proliferation. The antimetabolite drug 5-fluorouracil (5-FU) is an extensively used anticancer agent; however, its major limitation is the lack of target specificity. Cyanine 5 (Cy5), a fluorescent probe, can be used to label DNA tetrahedron and enhance photostability with minimal effects on its basic functions. In this study, we additionally attached 5-FU to the DNA-based delivery system as a new tumor-targeting nanomedicine (AS1411-T-5-FU) to enhance the therapeutic efficacy and targeting of breast cancer. We examined the difference of the cellular uptake of AS1411-T-5-FU between breast cancer cells and normal breast cells and concluded that AS1411-T-5-FU had a better targeting ability to kill breast cancer cells than 5-FU. We further evaluated the expressions of cell apoptosis-related proteins and genes, which are associated with the mitochondrial apoptotic pathway. Ultimately, our results suggest the potential of DNA tetrahedron in cancer therapies, and we develop a novel approach to endow 5-FU with targeting property.

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

“…Previous studies have indicated that tFNAs can promote the proliferation of various cell types. 24 – 27 , 29 , 34 , 35 Therefore, in this research, we aimed to determine whether this type of effect also existed in HaCaT and HSF cells. CCK-8 assays were used to examine cell proliferation, while cell-cycle assays were used to analyze changes in the number of cells at each stage.…”

“…As shown in previous studies, tFNAs are able to promote cell migration. 27 – 29 , 35 Scratch experiments are widely performed to investigate cell migration in vitro, but there are still factors that can interfere with these outcomes. In this study, to minimize variability, all scratches were made by the same person.…”

Tetrahedral DNA nanostructures as drug delivery and bioimaging platforms in cancer therapy

“…B, AS1411 aptamer‐modified TDN for selective 5‐fluorouracil (5‐FU) delivery to breast cancer cells. Reproduced with permission 52 . C, Methylene blue (MB)‐loaded TDN for in vitro and in vivo photodynamic therapy.…”

“…The same group also reported the use of AS1411‐aptamer‐modified TDN to deliver the antimetabolite 5‐fluorouracil to specific breast cancer cells (Figure 3B). 51 The modified TDN showed the effect on cell cycle and apoptotic genes and proteins. Moreover, Chen and coworkers developed the anticancer metal complex, [Ir(ppy) 2 phen] + PF 6 (Ir)‐loaded TDN, to inhibit vascular mimicry (VM) formation, which enhances tumor migration and metastasis in glioma 52 .…”

Functionalized selenium nanoparticles for targeted siRNA delivery silence Derlin1 and promote antitumor efficacy against cervical cancer

“…Chemotherapy drugs usually cause apoptosis of cancer cells via generating a large number of reactive oxygen species (ROS) (Zhan et al, 2019). Therefore, the ROS generation in HeLa cells was examined by fluorescence in this study.…”