14 September 2012

DNA origami will make toxic anti-cancer drug safe

Roman Ivanov, Computer

Researchers from the Karolinska Institute (Sweden) have demonstrated how DNA origami can enhance the effect of cytostatics in anti-cancer therapy. Using modern nanotechnology, scientists have been able to deliver a drug to a tumor without affecting the surrounding healthy tissues.

Doxorubicin has been used for a long time in anti-cancer therapy as an effective cytostatic agent, a substance that prevents cell division. Alas, its use is severely limited by unpleasant side effects, in which the patient's heart primarily suffers (the drug is toxic to heart muscle cells and can easily cause it to stop). That is why the issue of targeted delivery of the active substance directly to the tumor cells is particularly acute. One of the possible solutions that is most hoped for is the use of nanoparticles loaded with a drug.

In a study, the results of which are presented in the journal ACS Nano (Zhao et al., DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties), Swedish scientists have shown that DNA origami can be used as a carrier of doxorubicin. DNA origami is a relatively new technique for constructing volumetric nanostructures from DNA molecules, a hereditary material present in cell nuclei. With its application, it becomes possible to produce rather complex nanostructures with surfaces to which a variety of molecules and proteins can be attached (which is very difficult in the case of inorganic nanoparticles).

So, doxorubicin was packed inside origami from "uncoiled" DNA double helices (in other words, from molecules with a reduced degree of twisting), which made it possible to slow down the rate of release of the drug and, consequently, increase its effectiveness when acting on tumor cells. At the same time, the drug concentrations used were almost record low.

The doxorubicin molecule (left) is placed inside a DNA origami with a surface modified for selective interaction with cancer cells (right). (Illustration ACS.)

What is the reason for this? With a lower degree of DNA twisting, more places appear that can hold the doxorubicin molecule, which generally reduces the rate of release of the substance outside (kinetic control). Another advantage of DNA origami is that its surface is very easy to modify for a specific protein target, thereby ensuring the highest degree of selectivity at which healthy cells can feel completely safe.

Prepared based on the materials of the Karolinska Institute.

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