Researchers Kill Drug-Resistant Leukemia Cells Using DNA "Trojan Horse" Attack

Your days are up, leukemia. Giovanni Cancemi/Shutterstock

Getting cancer-killing drugs to go exactly where they’re needed in the body is fraught with difficulty. New methods are being tested all the time, and it’s becoming increasingly clear that the field of nanotechnology may provide some workable answers. With this in mind, a new study in the journal Small has used a nanosized “Trojan horse” in order to smuggle drugs into highly resistant cancer cells.

Researchers at Ohio State University were treating acute myeloid leukemia (AML) cells within mice with the chemotherapy drug daunorubicin. Some of these cells were entirely resistant to this type of treatment: When molecules of this drug enter an AML cell, they quickly respond and pump it back out through small openings in their cell walls.

To overcome this issue, the researchers had to conjure up a way to smuggle it in without the cell noticing. They thought that an incredibly small structure might be able to successfully conceal the drug, and so they turned to DNA.

 

 

One of the capsules infiltrating and releasing its contents inside an AML cell. Halley et al./Ohio State University

The team showed that, by carefully manipulating strands of viral DNA, an origami structure with complex folds can be created in just 10 minutes. Incredibly, these structures are only 100 nanometers across – that’s 1,000 times smaller than the width of a human hair. Small volumes of daunorubicin can be wrapped up in these minuscule pods, which can then be released into a leukemia cell-filled environment.

White blood cells, including the types involved in AML, are roughly 20 times smaller than the width of a human hair. This may seem small, but this is equivalent to 100 DNA origami structures. It is this huge size difference that makes them the ideal Trojan horse for smuggling in chemotherapy drugs.

These strong, stable, rod-shaped capsules were seen to infiltrate the AML cells, retrieved from their surroundings as if they were nutrients. When a capsule is sufficiently deep inside the cell, it begins to break down, and the anti-cancer drugs are released. The AML cell can’t react in time to pump the drug back out, and it promptly dies.

The origami structures, both empty (left) and loaded with a chemotherapy drug (right). Randy Patton/Ohio State University

At present, these origami capsules could potentially be absorbed by non-threatening cells. “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,” said study coauthor John Byrd, a professor of internal medicine at the Ohio State University Wexner Medical Center, in a statement.

This new technique, while still at the proof-of-concept stage, is another addition to the growing collection of nanoscale chemotherapy treatments. Researchers have previously shown that genetically engineered algae are able to act as drug-delivery “backpacks” that can actively target specific cells. Graphene, the veritable wonder material, has also been used: Small shards of it are remotely heated up when they encounter a tumor, annihilating parts of it.

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