Modulation of chondrocyte motility by tetrahedral DNA nanostructures

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Contemporarily, a highly increasing attention was paid to nanoconstructs, particularly DNA nanostructures possessing precise organization, functional manipulation, biocompatibility and biodegradability. Amongst these DNA nanomaterials, tetrahedral DNA nanostructures ( TDN s) are a significantly ideal bionanomaterials with focusing on the property that can be internalized into cytoplasm in the absence of transfection. Therefore, the focus of this study was on investigating the influence of TDN s on the chondrocytes locomotion. Tetrahedral DNA nanostructures was confirmed by 6% polyacrylamide gel electrophoresis ( PAGE ) and dynamic light scattering ( DLS ). Subsequently, the effect of TDN s on chondrocyte locomotion was investigated by real‐time cell analysis ( RTCA ) and wound healing assay. The variation of relevant genes and proteins was detected by quantitative polymerase chain reaction ( qPCR ), western blotting and immunofluorescence respectively. We demonstrated that tetrahedral DNA nanostructures have positive influence on chondrocytes locomotion and promoted the expression of RhoA , ROCK 2 and vinculin . Additionally, upon exposure to TDN s with the concentration of 250 nmol L −1 , the chondrocytes were showed the highest motility via both RTCA and wound healing assay. Meanwhile, the mRNA and protein expression of RhoA, ROCK 2 and vinculin were also significantly enhanced with the same concentration. It can be concluded that the TDN s with the optimal concentration of 250 nmol L −1 could extremely promoted the chondrocytes locomotion through facilitating the expression of RhoA , ROCK 2 and vinculin . These results seemed to reveal that this special three‐dimensional DNA tetrahedral nanostructures may be applied to cartilage repair and treatment in the future.

Related collections

Most cited references 42

Record: found
Abstract: found
Article: not found

Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted In Vivo siRNA Delivery

Hyukjin Lee, Abigail K. R. Lytton-Jean, Yi Chen … (2012)

Nanoparticles are employed for delivering therapeutics into cells 1,2 . However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell specific internalization, excretion, toxicity, and efficacy 3-7 . A variety of materials have been explored for delivering small interfering RNAs (siRNAs) - a therapeutic agent that suppresses the expression of targeted genes 8,9 . However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, lack of tissue specificity and potential toxicity 10-12 . Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer targeting ligands (such as peptides and folate) on the nanoparticle surface can be precisely controlled. We show that at least three folate molecules per nanoparticle is required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t1/2 ∼ 24.2 min) than the parent siRNA (t1/2 ∼ 6 min).

0 comments Cited 330 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication.

R P Goodman (2005)

Practical components for three-dimensional molecular nanofabrication must be simple to produce, stereopure, rigid, and adaptable. We report a family of DNA tetrahedra, less than 10 nanometers on a side, that can self-assemble in seconds with near-quantitative yield of one diastereomer. They can be connected by programmable DNA linkers. Their triangulated architecture confers structural stability; by compressing a DNA tetrahedron with an atomic force microscope, we have measured the axial compressibility of DNA and observed the buckling of the double helix under high loads.

0 comments Cited 243 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

DNA origami as a carrier for circumvention of drug resistance.

Qiao Jiang, Chen Song, Jeanette Nangreave … (2012)

Although a multitude of promising anti-cancer drugs have been developed over the past 50 years, effective delivery of the drugs to diseased cells remains a challenge. Recently, nanoparticles have been used as drug delivery vehicles due to their high delivery efficiencies and the possibility to circumvent cellular drug resistance. However, the lack of biocompatibility and inability to engineer spatially addressable surfaces for multi-functional activity remains an obstacle to their widespread use. Here we present a novel drug carrier system based on self-assembled, spatially addressable DNA origami nanostructures that confronts these limitations. Doxorubicin, a well-known anti-cancer drug, was non-covalently attached to DNA origami nanostructures through intercalation. A high level of drug loading efficiency was achieved, and the complex exhibited prominent cytotoxicity not only to regular human breast adenocarcinoma cancer cells (MCF 7), but more importantly to doxorubicin-resistant cancer cells, inducing a remarkable reversal of phenotype resistance. With the DNA origami drug delivery vehicles, the cellular internalization of doxorubicin was increased, which contributed to the significant enhancement of cell-killing activity to doxorubicin-resistant MCF 7 cells. Presumably, the activity of doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites. Our results suggest that DNA origami has immense potential as an efficient, biocompatible drug carrier and delivery vehicle in the treatment of cancer.