DNA origami as a carrier for circumvention of drug resistance

Qiao Jiang, Chen Song, Jeanette Nangreave, Xiaowei Liu, Lin Lin, Dengli Qiu, Zhen Gang Wang, Guozhang Zou, Xingjie Liang, Hao Yan, Baoquan Ding

Research output: Contribution to journalArticle

376 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13396-13403
Number of pages8
JournalJournal of the American Chemical Society
Volume134
Issue number32
DOIs
Publication statusPublished - Aug 15 2012

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Jiang, Q., Song, C., Nangreave, J., Liu, X., Lin, L., Qiu, D., Wang, Z. G., Zou, G., Liang, X., Yan, H., & Ding, B. (2012). DNA origami as a carrier for circumvention of drug resistance. Journal of the American Chemical Society, 134(32), 13396-13403. https://doi.org/10.1021/ja304263n