One of the most successful techniques to combat multidrug resistance in cancer cells is the downregulation of those genes responsible for drug resistance. Chinese scientists have now developed a nanoplatform that selectively delivers small hairpin RNA transcription templates and chemotherapeutics into multidrug-resistant tumors. A deadly cocktail of gene-silencing elements and chemotherapeutic drugs effectively and selectively kills cells, they reported in the journal Angewandte Chemie. The nanoplatform was assembled using established DNA origami techniques.
Multidrug-resistant cancer cells often remove potent drugs from the cell before they can become effective. As several genes for proteins that perform this job are known, scientists attempt to interfere on the gene expression level, which is possible with RNA interference (RNAi) techniques: small RNAi strands combine with messenger RNA and inhibit transcription. However, RNA transcription templates must be delivered and released into the cytoplasm of the cell, and at the same time, a potent drug must be present to kill the cell.
Baoquan Ding at the National Center for Nanoscience and Technology, Beijing, China, and his colleagues have now designed and built a platform that includes every item needed to intrude into tumor cells and release gene-silencing elements and chemotherapeutic drugs. They built the platform using the DNA origami technique, which allows the construction of nanosized DNA objects in multiple, and even very complicated shapes. In this case, the scientists constructed a relatively simple DNA origami structure, which self-assembled into a triangular nanoplatform with various sites to bind multiple functional units.
One of the key features of the platform was that it could include the hydrophobic potent drug doxorubicin (DOX), a cytostatic that is especially useful against malign tumors. Here, DOX did not bind to the nanoplatform by any covalent linkage, but was loaded onto it through intercalation (which is the way DOX works in the cell: it intercalates into DNA, inhibiting transcription). Instead, what was covalently linked to the platform was the multiple gene silencing and cell-targeting site, which consisted of two linear small hairpin RNA transcription templates for RNAi and gene therapy, a cell-specific unit for specific recognition and insertion by the tumor cell, and a disulfide linkage to be cleaved by cellular glutathione.
The authors examined their multipurpose nanoplatform with an in vitro assay (on cell cultures) and by administering it into mice containing multidrug-resistant tumors. They found both a high and selective delivery and release rate of DOX and RNA transcription templates, and a high and selective tumor-killing efficiency. In addition, the multifunctional platform itself was not harmful to mice; however, filled with drugs and delivery sites, it was effective and deadly to multidrug-resistant tumors, the authors reported.
This research demonstrates what is possible in cancer therapy. The scientists have designed a nanostructure that not only specifically targets cancer cells, thus reducing severe side effects in chemotherapy, but also carries a drug and everything needed to suppress resistance in the cell when releasing the drug. And the platform itself is modifiable; adaption to other delivery strategies and other therapeutic components is easily possible, according to the authors.
The Latest on: DNA origami
via Google News
The Latest on: DNA origami
- DNA computers will solve specific types of problemson October 10, 2021 at 6:19 pm
DNA computers will solve specific types of problems DNA or Deoxyribonucleic Acid based computers offer a new way of processing data. They seem to offer an alternative solution as speed of ...
- DNA Origami Market Overview by Type, Structure, Application and Regional Insights 2020-2028on October 6, 2021 at 11:51 pm
DNA origami refers to the nanoscale folding of DNA to create 2D or 3D shapes at nanoscale such as nanorobots that can work as smart drugs when successfully delivered to cells. DNA origami ...
- When James Webb launches, it will have a bigger to-do list than 1980s researchers suspectedon October 6, 2021 at 8:05 pm
“They call this the origami satellite,” says astronomer Scott Friedman of the Space Telescope Science Institute, or STScI, in Baltimore. Friedman is in charge of Webb’s postlaunch choreography.
- Steve Jobs' 23-year-old daughter Eve makes her runway debut Coperni's Paris Fashion Week showon October 1, 2021 at 2:32 pm
Coperni's collection included a new bag that was aptly inspired by the iPhone photos app icon — the 'Origami' — according to Vogue. The Apple heiress shared behind-the-scenes photos from ...
- 3D Pictures of Huge, Self-Assembled DNA Structureson September 21, 2021 at 5:00 pm
You can see those in this video, which also shows models of the polyhedral structures. This time, Yin's team is using a method known as DNA origami to make the building blocks; his earlier work used ...
- Martin A. Fisher School of Physicson September 20, 2021 at 5:00 pm
Daichi Hayakawa, Brandeis University Host: John Wardle "Programming the self-assembly of tubules using DNA origami triangles as building blocks" Abstract: DNA origami is a method by which a ...
- Breakthrough Research May Help Reduce Viral Load in Infectionson September 20, 2021 at 1:20 pm
Fraden says Dietz’s Technical University of Munich team are world leaders in the nanobiotechnology field known as “DNA origami,” or designing DNA that can fold to create complex 3D forms. “Combining ...
- DNA Strands Used to Create Complicated Branching Structureson September 15, 2021 at 5:00 pm
Scientists from Brigham Young University have been developing new “DNA origami” techniques to create complicated structures that were previously impossible. Using PCR amplification they were ...
- Structural DNA Nanotechnologyon September 15, 2021 at 8:46 am
Written by the founder of the field, this is the first text of its kind, providing a definitive introduction to structural DNA nanotechnology. Readers will learn everything there is to know about the ...
via Bing News