Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells

Le Liang, Jiang Li, Qian Li, Qing Huang, Jiye Shi, Hao Yan, Chunhai Fan

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

DNA is typically impermeable to the plasma membrane due to its polyanionic nature. Interestingly, several different DNA nanostructures can be readily taken up by cells in the absence of transfection agents, which suggests new opportunities for constructing intelligent cargo delivery systems from these biocompatible, nonviral DNA nanocarriers. However, the underlying mechanism of entry of the DNA nanostructures into the cells remains unknown. Herein, we investigated the endocytotic internalization and subsequent transport of tetrahedral DNA nanostructures (TDNs) by mammalian cells through single-particle tracking. We found that the TDNs were rapidly internalized by a caveolin-dependent pathway. After endocytosis, the TDNs were transported to the lysosomes in a highly ordered, microtubule-dependent manner. Although the TDNs retained their structural integrity within cells over long time periods, their localization in the lysosomes precludes their use as effective delivery agents. To modulate the cellular fate of the TDNs, we functionalized them with nuclear localization signals that directed their escape from the lysosomes and entry into the cellular nuclei. This study improves our understanding of the entry into cells and transport pathways of DNA nanostructures, and the results can be used as a basis for designing DNA-nanostructure-based drug delivery nanocarriers for targeted therapy. Transported to a better place: The endocytotic internalization of tetrahedral DNA nanostructures (TDNs) into cells by a caveolin-dependent pathway was investigated through single-particle tracking. The subsequent microtubule-dependent transport of the TDNs to the lysosomes for digestion (see figure) could be redirected to the nucleus by functionalization of the TDNs.

Original languageEnglish
Pages (from-to)7745-7750
Number of pages6
JournalAngewandte Chemie - International Edition
Volume53
Issue number30
DOIs
Publication statusPublished - Jul 21 2014

Fingerprint

Cell Tracking
Nanostructures
DNA
Modulation
Lysosomes
Caveolins
Microtubules
Nuclear Localization Signals
Structural integrity
Cell membranes
Endocytosis

Keywords

  • cell internalization
  • cell transport
  • DNA structures
  • nanostructures
  • single-particle tracking

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Medicine(all)

Cite this

Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells. / Liang, Le; Li, Jiang; Li, Qian; Huang, Qing; Shi, Jiye; Yan, Hao; Fan, Chunhai.

In: Angewandte Chemie - International Edition, Vol. 53, No. 30, 21.07.2014, p. 7745-7750.

Research output: Contribution to journalArticle

Liang, Le ; Li, Jiang ; Li, Qian ; Huang, Qing ; Shi, Jiye ; Yan, Hao ; Fan, Chunhai. / Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells. In: Angewandte Chemie - International Edition. 2014 ; Vol. 53, No. 30. pp. 7745-7750.
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