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A way to protect DNA origami has been found
Scientists have developed and synthesized molecules with precise sequence and length to effectively protect three-dimensional DNA nanostructures from destruction. The results of the work are published in the Proceedings of the National Academy of Sciences.
Similar to the Japanese art of paper folding, DNA origami is giving long flexible DNA chains the desired shape by "stitching" different parts of the chain with complementary base pairs. Such nanoscale structures can be useful for many biomedical applications, including targeted delivery of drugs and genes to desired tissues or cells, visualization of biological processes inside the body and the creation of biosensors. However, such use of these molecular structures requires protection of DNA origami from changes in biological fluids, which may entail the inclusion of non-target functions.
Experts at Brookhaven National Laboratory have found one way to increase the stability of DNA-origami. To do this, they synthesized biocompatible molecules called peptoids with a well-defined length and molecular composition of the sequence. Peptoids are non–peptide molecules that have a similar structure to them and act as regulatory peptides.
Scientists have coated them with DNA origami in the form of an octahedron, which itself has high mechanical stability and a large open space for transporting nanoscale cargo, such as low-molecular-weight anti-cancer drugs. The authors also showed that peptoid coatings effectively protect DNA origami under various physiological conditions and can be used to add various chemical functions necessary for use in biomedicine.
DNA origami with a protective peptoid coating reduces trypsin hydrolysis of encapsulated bovine serum albumin labeled with fluorophore (BSA). Figure from the press release of Brookhaven National Laboratory Protecting DNA Origami for Anti-Cancer Drug Delivery – VM.
The researchers studied the structural stability of the DNA origami coated with peptoids in several types of physiological conditions: in a solution containing a low concentration of positively charged magnesium ions in a solution with a DNA-specific nuclease, and in media with cell cultures containing both nucleases and magnesium ions. As a rule, a high concentration of Mg ions is necessary to stabilize DNA origami by reducing the repulsion between the two molecules, but physiological fluids contain much lower concentrations that do not produce such an effect.
The results showed that the structure of DNA origami remained exactly the same in any physiological environment if they were previously coated with peptoids. Now the researchers intend to study the effectiveness of combination therapy, which includes peptoid-functionalized DNA origami with doxorubicin and trastuzumab. Such therapy will target HER2-positive breast cancer cells.
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