Scientists from Ohio State University are working on a DNA "Trojan horse" that hides the invading force, in this case a cancer drug, and it could become a new way to treat cancers that are typically resistant to drug treatment.
In the recent laboratory tests, the team showed that leukemia cells that were resistant to a particular drug absorbed it and died when it was hidden in a capsule of folded up DNA. Although previous research has taken advantage of this same technique, also called "DNA origami," this is the first time that it has been shown to work on drug-resistant leukemia cells. The team is now testing the capsule in mice and hopes to conduct clinical trials on humans within a few years.
The study examined a pre-clinical model of acute myeloid leukemia (AML) that developed resistance to the drug daunorubicin. When the drug molecules entered the AML cell, the cell recognized them and pushed them back out through pumps in the wall.
"Cancer cells have novel ways of resisting drugs, like these pumps, and the exciting part of packaging the drug this way is that we can circumvent those defences so that the drug accumulates in the cancer cell and causes it to die," John Byrd, co-author of the study, said in a press release. "Potentially, we can also tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects."
Once hidden inside tiny rod-shaped DNA capsules, the AML cells that previously resisted the daunorubicin molecules effectively absorbed them.
"DNA origami nanostructures have a lot of potential for drug delivery, not just for making effective drug delivery vehicles, but enabling new ways to study drug delivery. For instance, we can vary the shape or mechanical stiffness of a structure very precisely and see how that affects entry into cells," said Carlos Castro, who also co-authored the study.
If the work is effectively translated into an animal model, the technique could be used on almost any form of drug-resistant cancer, although it may not be effective against other pathogens such as bacteria due to the unique mechanisms of drug resistance that they utilize.
The findings were published in the Jan. 14 issue of Small.
