Overcoming drug-resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures

Abstract

Paclitaxel (PTX) is an effective drug against diseases such as lung cancer, ovarian cancer, and breast cancer. However, multidrug resistance limits the clinical applications of this drug. Tetrahedral DNA nanostructures (TDNs) offer great promise as a drug delivery candidate. In our study, we prepared TDNs that were subsequently loaded with PTX (PTX/TDNs). The cytotoxicity of PTX/TDNs and PTX alone on non-small cell lung cancer (NSCLC) cells (A549) and the PTX-resistant cell line (A549/T) was determined using a cell count kit-8 (CCK-8) assay. PTX/TDNs exerted strong lethality on both cell lines. Moreover, drug resistance was overcome. Furthermore, the mechanisms used by PTX/TDNs to overcome drug resistance were studied. The expression of mdr 1 gene and P-glycoprotein (P-gp) in A549/T was found to be downregulated, thus indicating that TDNs serve as a P-gp inhibitor. We also showed that PTX/TDNs killed cancer cells via apoptosis. Thus, PTX/TDNs have great potential for use as a nanodelivery system for the treatment of PTX-resistant NSCLC.

Tetrahedral DNA nanostructures facilitate neural stem cell migration via activating RHOA/ROCK2 signalling pathway

“…Therefore, TDNs possess excellent structural stability, mechanical rigidity and modification versatility . Previous studies of TDNs have shown that different cells could internalize TDNs, and then TDNs exerted influence on the cells’ biological behaviours under certain conditions . For instance, TNDs could maintain the chondrocyte phenotype, promote chondrocyte proliferation and accelerate dental pulp stem cells osteo/odontogenic differentiation .…”

Tetrahedral Framework Nucleic Acids Promote Corneal Epithelial Wound Healing in Vitro and in Vivo

“…Recently, DNA nanotechnology has been developed and employed in a variety of fields owing to the extensive biological functions of DNA nanostructures . Tetrahedral framework nucleic acids (tFNAs) are synthesized by four isometric single‐stranded DNAs through a simple, rapid, and reliable process, which have been identified as 3D DNA nanostructures with a stable structure and superior mechanical properties . Many biological functions can be affected after tFNAs are transported into cells, including osteogenic differentiation, nerve tissue regeneration, anti‐inflammatory, and antioxidant effects .…”

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

“…Multiple analytical techniques can be applied for verification and characterization of successful TDN construction. So far, gel electrophoresis in a nondenaturing condition is the simplest procedure used to confirm designed cDNA binding by visualizing band shift 14‐20 . The dynamic light scattering technique has been widely used to determine the size and zeta‐potential of TDN 15,21‐23 and the homogeneity of the nanostructures in solution as it directly measures the hydrodynamic size in a precise nanometer range 24 .…”

“…Xie and coworkers investigated the effects of paclitaxel (PTX)‐loaded TDN on PTX‐resistant non‐small‐cell lung cancer cells and found that PTX‐loaded TDN can overcome drug resistance by downregulating the expression of mdr1 gene and P‐glycoprotein, resulting in reduced drug efflux from cancer cells 16 . 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).…”