Oncology Central

DNA origami nanostructures could bypass drug resistance in leukemia cells

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Recently published in Small, researchers from The Ohio State University (OSU; OH, USA) have developed DNA origami nanoparticles encasing anthracycline drugs that could potentially be used to circumvent drug resistance in daunorubicin-refractory acute myeloid leukemia.

John Byrd (Wexner Medical Center, OSU) and Carlos Castro (Department of Mechanical and Aerospace Engineering, OSU), collaborated on developing these DNA origami nanostructures using bacteriophage DNA to produce capsules to deliver the chemotherapeutic drugs via endocytosis, thus evading the resistance mechanisms of the cancer cells.

“Cancer cells have novel ways of resisting drugs…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” stated Byrd.

The 15 x 100 nm DNA nanostructures use the bacteriophage DNA as a transport medium with many accessible base pairs to maximize surface area availability to carry the drug. Once transported into the cancer cell, the origami structure breaks down allowing the anthracycline to bind to the cell’s DNA, preventing further cellular replication.

Castro and his team formed these capsules for stability, to ensure that the nanostructure would not break down completely and release the majority of their drug cargo until the cell’s resistance mechanism had been nullified.

If this system exhibits positive results when translated to other cancer cell types, it could be an exciting development in drug delivery across a wide range of cancers.

Byrd also stated: “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,” Castro commented, as he hopes to develop an economically viable process for producing these capsules as a drug delivery system.

Sources: Halley PD, Lucas CR, McWilliams EM et al. DNA Origami: Daunorubicin-Loaded DNA Origami Nanostructures Circumvent Drug-Resistance Mechanisms in a Leukemia Model (Small 3/2016). Small, 12 (3), 307 (2016); The Ohio State University press release

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