Targeted drug delivery to leukemia cells using DNA origami
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Date
2017-05
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The Ohio State University
Abstract
An estimated 600,000 Americans will die from cancer in 2017. Acute myeloid leukemia (AML) is a particularly deadly form of cancer, with a five-year survival rate of only 26 percent. Chemotherapy, currently the frontline treatment method, has two main limitations: cancer cells can develop drug resistances and the drugs harm healthy cells as well as cancer cells. Currently no FDA-approved targeted therapies exist for AML. The purpose of this project is to develop an effective nanoparticle based cancer drug delivery device that can target and destroy AML cells. DNA nanostructures have recently garnered attention as a novel method for cancer drug delivery due to the precise control they allow over nanostructure geometry. It has recently been shown that when daunorubicin, a drug widely used to treat AML, is attached to DNA nanostructures, the nanostructures allow the drug to circumvent developed drug resistance in cancer cells. Therefore, we hypothesize that building a targeted version of these DNA drug delivery devices could lead to an effective treatment for AML and other cancers. We developed a method that uses the specificity of antibody-antigen interactions to use DNA origami to target CD33 antigens on HL-60 AML cells. We utilized the highly precise geometry of DNA origami to attach anti-CD33 antibodies to specific locations on a nanostructure, to prevent non-target cell interactions. Fluorescent microscopy experiments showed that when the anti-CD33 antibody is attached to a DNA nanostructure, without cancer drugs and in the presence of other cell types, the nanostructure preferentially bound to the cell membranes of HL-60 AML cells. Drug-loaded experiments have not yet shown conclusive evidence, and more experiments need to be performed to ascertain if the drug affects targeting. We believe the drug may not be attached strongly enough to the nanostructure and the design may need to be altered. However, the promising targeting results we have obtained suggest DNA origami has strong potential as a cancer drug delivery device that can potentially simultaneously circumvent drug resistance and target cancer cells.
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Keywords
DNA, origami, leukemia, targeted, delivery