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

331 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 (US)
Pages (from-to)13396-13403
Number of pages8
JournalJournal of the American Chemical Society
Volume134
Issue number32
DOIs
StatePublished - Aug 15 2012

Fingerprint

Drug Carriers
Drug Resistance
DNA
Doxorubicin
Pharmaceutical Preparations
Drug delivery
Nanostructures
MCF-7 Cells
Cells
Neoplasms
Acidification
Cytotoxicity
Intercalation
Biocompatibility
Nanoparticles
Engineers
Adenocarcinoma
Breast Neoplasms
Phenotype

ASJC Scopus subject areas

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

Cite this

Jiang, Q., Song, C., Nangreave, J., Liu, X., Lin, L., Qiu, D., ... 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

DNA origami as a carrier for circumvention of drug resistance. / Jiang, Qiao; Song, Chen; Nangreave, Jeanette; Liu, Xiaowei; Lin, Lin; Qiu, Dengli; Wang, Zhen Gang; Zou, Guozhang; Liang, Xingjie; Yan, Hao; Ding, Baoquan.

In: Journal of the American Chemical Society, Vol. 134, No. 32, 15.08.2012, p. 13396-13403.

Research output: Contribution to journalArticle

Jiang, Q, Song, C, Nangreave, J, Liu, X, Lin, L, Qiu, D, Wang, ZG, 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, vol. 134, no. 32, pp. 13396-13403. https://doi.org/10.1021/ja304263n
Jiang Q, Song C, Nangreave J, Liu X, Lin L, Qiu D et al. DNA origami as a carrier for circumvention of drug resistance. Journal of the American Chemical Society. 2012 Aug 15;134(32):13396-13403. https://doi.org/10.1021/ja304263n
Jiang, Qiao ; Song, Chen ; Nangreave, Jeanette ; Liu, Xiaowei ; Lin, Lin ; Qiu, Dengli ; Wang, Zhen Gang ; Zou, Guozhang ; Liang, Xingjie ; Yan, Hao ; Ding, Baoquan. / DNA origami as a carrier for circumvention of drug resistance. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 32. pp. 13396-13403.
@article{c21d1d561c744d019131cdcf7001e0b1,
title = "DNA origami as a carrier for circumvention of drug resistance",
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.",
author = "Qiao Jiang and Chen Song and Jeanette Nangreave and Xiaowei Liu and Lin Lin and Dengli Qiu and Wang, {Zhen Gang} and Guozhang Zou and Xingjie Liang and Hao Yan and Baoquan Ding",
year = "2012",
month = "8",
day = "15",
doi = "10.1021/ja304263n",
language = "English (US)",
volume = "134",
pages = "13396--13403",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "32",

}

TY - JOUR

T1 - DNA origami as a carrier for circumvention of drug resistance

AU - Jiang, Qiao

AU - Song, Chen

AU - Nangreave, Jeanette

AU - Liu, Xiaowei

AU - Lin, Lin

AU - Qiu, Dengli

AU - Wang, Zhen Gang

AU - Zou, Guozhang

AU - Liang, Xingjie

AU - Yan, Hao

AU - Ding, Baoquan

PY - 2012/8/15

Y1 - 2012/8/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865121664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865121664&partnerID=8YFLogxK

U2 - 10.1021/ja304263n

DO - 10.1021/ja304263n

M3 - Article

VL - 134

SP - 13396

EP - 13403

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 32

ER -