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August 20, 2012

DNA Origami as a Carrier for Circumvention of Drug Resistance

New Scientist - DNA Origami Trojan horse was used delivered a dose of the drug that proved lethal to human breast-cancer cells, even though they had developed resistance to doxorubicin. "This is the first study to demonstrate that DNA origami can be used to circumvent drug resistance," says Hao Yan at Arizona State University in Tempe, who jointly led the work. The cancer cells may not recognise the DNA origami as a threat in the way that free doxorubicin is, he suggests. The folded DNA might also alter the pH inside the cells, increasing the drug's activity.

Journal of the American Chemical Society - DNA Origami as a Carrier for Circumvention of Drug Resistance

Although a multitude of promising anti-cancer drugs have been developed over the past 50 years, effective delivery of the drugs to diseased cells remains a challenge. Recently, nanoparticles have been used as drug delivery vehicles due to their high delivery efficiencies and the possibility to circumvent cellular drug resistance. However, the lack of biocompatibility and inability to engineer spatially addressable surfaces for multi-functional activity remains an obstacle to their widespread use. Here we present a novel drug carrier system based on self-assembled, spatially addressable DNA origami nanostructures that confronts these limitations. Doxorubicin, a well-known anti-cancer drug, was non-covalently attached to DNA origami nanostructures through intercalation. A high level of drug loading efficiency was achieved, and the complex exhibited prominent cytotoxicity not only to regular human breast adenocarcinoma cancer cells (MCF 7), but more importantly to doxorubicin-resistant cancer cells, inducing a remarkable reversal of phenotype resistance. With the DNA origami drug delivery vehicles, the cellular internalization of doxorubicin was increased, which contributed to the significant enhancement of cell-killing activity to doxorubicin-resistant MCF 7 cells. Presumably, the activity of doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites. Our results suggest that DNA origami has immense potential as an efficient, biocompatible drug carrier and delivery vehicle in the treatment of cancer.


This work was presented on April 12, 2012 at the Materials Research Society Symposium on DNA Nanotechnology



11 pages of supporting information


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