DNA ‘Trojan horse’ smuggles drugs into resistant cancer cells

Posted: February 25, 2016

Cells mistake DNA casing for food, consume drugs and die






John Byrd
John Byrd



He and Carlos Castro, assistant professor of mechanical engineering, lead a collaboration focused on hiding daunorubicin inside a kind of molecular Trojan horse that can bypass the pumps so they can’t eject the drug from the cell.

Carlos Castro
Carlos Castro

“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 defenses so that the drug accumulates in the cancer cell and causes it to die,” said Byrd, a professor of internal medicine and director of the Division of Hematology. “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.”

“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 Castro, director of the Laboratory for Nanoengineering and Biodesign.


Each capsule measures about 15 nanometers wide and 100 nanometers long—about 100 times smaller than the cancer cells it’s designed to infiltrate. With four hollow, open-ended interior compartments, it looks less like a pill a human would swallow and more like an elongated cinder block.

Postdoctoral researcher Christopher Lucas said that the design maximizes the surface area available to carry the drug. “The way daunorubicin works is it tucks into the cancer cell’s DNA and prevents it from replicating. 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.”

Castro’s team designed the capsules to be strong and stable, so that they wouldn’t fully disintegrate and release the bulk of the drugs until it was too late for the cell to spit them back out.

And that’s what they saw with a fluorescence microscope—the cells drew the capsules into the organelles that would normally digest them, if they were food. When the capsules broke down, the drugs flooded the cells and caused them to disintegrate. Most cells died within the first 15 hours after consuming the capsules.

This work is the first effort for the engineers in Castro’s lab to develop a medical application for the DNA origami structures they have been building.

Though DNA is stereotypically called the “building blocks of life,” engineers today use natural and synthetic DNA as literal building blocks for mechanical devices. Previously, the Ohio State engineers created tiny hinges and pistons of DNA.

As Castro pointed out, DNA is a polymer—albeit a naturally occurring one—and he and his colleagues shape it into tiny devices, tools or containers by exploiting the physical interactions of the bases that make up the polymer chain. They build chains from DNA sequences that will naturally attract and bind with one another in certain ways, so that long the long polymers automatically fold up, or “self-assemble,” into useful shapes.


“One of the hardest things to get across when you’re introducing this technology to people is that the DNA capsule doesn’t do anything except hold a shape. It’s just a static, rigid structure that carries things. It doesn’t encode any proteins or do anything else that we normally think of DNA as doing,” Halley said.

In keeping with the idea of DNA origami manufacturing, Castro said he hopes to create a streamlined and economically viable process for building the capsules—and other shapes as well—as part of a modular drug delivery system.



by Pam Frost Gorder, Research Communications

Categories: FacultyResearch