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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 circu... Full description

Journal Title: Journal of the American Chemical Society 15 August 2012, Vol.134(32), pp.13396-403
Main Author: Jiang, Qiao
Other Authors: Song, Chen , Nangreave, Jeanette , Liu, Xiaowei , Lin, Lin , Qiu, Dengli , Wang, Zhen-Gang , Zou, Guozhang , Liang, Xingjie , Yan, Hao , Ding, Baoquan
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1520-5126 ; PMID: 22803823 Version:1 ; DOI: 10.1021/ja304263n
Link: http://pubmed.gov/22803823
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recordid: medline22803823
title: DNA origami as a carrier for circumvention of drug resistance
format: Article
creator:
  • Jiang, Qiao
  • Song, Chen
  • Nangreave, Jeanette
  • Liu, Xiaowei
  • Lin, Lin
  • Qiu, Dengli
  • Wang, Zhen-Gang
  • Zou, Guozhang
  • Liang, Xingjie
  • Yan, Hao
  • Ding, Baoquan
subjects:
  • Drug Delivery Systems
  • Antineoplastic Agents -- Chemistry
  • DNA Adducts -- Chemistry
  • Doxorubicin -- Chemistry
  • Drug Resistance, Neoplasm -- Drug Effects
  • Nanoparticles -- Chemistry
ispartof: Journal of the American Chemical Society, 15 August 2012, Vol.134(32), pp.13396-403
description: 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.
language: eng
source:
identifier: E-ISSN: 1520-5126 ; PMID: 22803823 Version:1 ; DOI: 10.1021/ja304263n
fulltext: no_fulltext
issn:
  • 15205126
  • 1520-5126
url: Link


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titleDNA origami as a carrier for circumvention of drug resistance
creatorJiang, Qiao ; Song, Chen ; Nangreave, Jeanette ; Liu, Xiaowei ; Lin, Lin ; Qiu, Dengli ; Wang, Zhen-Gang ; Zou, Guozhang ; Liang, Xingjie ; Yan, Hao ; Ding, Baoquan
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subjectDrug Delivery Systems ; Antineoplastic Agents -- Chemistry ; DNA Adducts -- Chemistry ; Doxorubicin -- Chemistry ; Drug Resistance, Neoplasm -- Drug Effects ; Nanoparticles -- Chemistry
descriptionAlthough 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.
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descriptionAlthough 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.
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abstractAlthough 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.
doi10.1021/ja304263n
pmid22803823
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date2012-08-15