Borrowing a page from history, a team of researchers from Ohio State University are working on a biological Trojan horse of sorts that can launch a sneak attack against cancer cells by hiding a commonly-used chemotherapy drug in a capsule made from folded-up DNA.
The packaging technique is known as “DNA origami,” and according to Dr. John Byrd, the chair of leukemia research at the OSU Wexner Medical Center, and mechanical engineering professor Carlos Castro, it has even proven effective at stopping drug-resistant cancer cells in lab tests.
DNA origami had previously been used to overcome drug resistance in solid tumors, but this is the first time that researchers have demonstrated that the technique can also be used on leukemia cells. The early results of their work have been published in the journal Small, and they are now testing the capsule in mice, with the hopes that human trials may soon follow.
In a statement, Castro explained that nanostructures made from DNA have demonstrated “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.”
Here’s a look at what the technique does to a cancer cell:
Technique could also prove effective against other forms of cancer
For their research, Castro and Dr. Byrd utilized a pre-clinical model of acute myeloid leukemia (AML) that had developed resistance against the anthracycline chemotherapy drug daunorubicin. In these cases, when daunorubicin molecules entered an AML cell, the cell is able to recognize them and eject them through openings in the cell wall.
By hiding the drug in a molecular Trojan horse, however, they can sneak it past the defenses of the AML cell, allowing it to accumulate within the cell and cause it to die, Dr. Byrd explained. He added that it should be possible to design these structures so that they target only cancer cells and not other parts of the body, potentially leading to harmful side effects.
Their tests found that AML cells which had previously demonstrated resistance to daunorubicin would absorb the drug molecules if they were hidden inside tiny, rod-shaped DNA capsules. At 15 nanometers wide and 100 nanometers long, each capsule was roughly one-percent the size of the cells it was designed to infiltrate, but tough enough to only disintegrate fully once they were fully consumed by the cells and it was too late for them to be ejected.
“The way daunorubicin works is it tucks into the cancer cell’s DNA and prevents it from replicating,” explained postdoctoral researcher Christopher Lucas. “So we designed a capsule structure that would have lots of accessible DNA base-pairs for it to tuck into. When the capsule breaks down, the drug molecules are freed to flood the cell.”
The majority of the cells died within the first 15 minutes after they consumed to capsules, the study authors said. Dr. Byrd believes that the technique should work on most forms of drug-resistant cancer, pending additional research, and Castro added that he hopes to create an easy to use and inexpensive way to mass produce these DNA capsules.
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Featured image: cells on the left are pre-treatment, post-treatment on the right. Image credit: Ohio State University
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