In vitro and in vivo behavior of DNA tetrahedrons as tumor-targeting nanocarriers for doxorubicin delivery

Ji Hee Kang, Kyoung Ran Kim, Hyukjin Lee, Dae Ro Ahn, Young Tag Ko

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Deoxyribonucleic acid (DNA) is a versatile material with high applicability and inherent biocompatibility. L-DNA, the perfect mirror form of the naturally occurring D-DNA, has been used in DNA nanotechnology. It has thermodynamically identical properties to D-DNA, is capable of self-assembly and bio-orthogonal base-pairing, and is resistant to nuclease activity. We previously constructed an L-DNA tetrahedron (L-Td) and found that this nanostructure has remarkably higher capacity for cell penetration than its natural counterpart (D-Td). L-Td molecules of two different sizes—one with 17-mer per side (L-Td17) and the other with 30-mer per side (L-Td30)—were prepared by assembling four L-DNA strands. In this study, cellular uptake of L-Td with different sizes was observed over time using a laser scanning confocal microscope (LSCM) equipped with a live cell chamber system. In addition, we conducted a pharmacokinetic study to examine the potential of L-Td as a carrier for in vivo tumor-targeted delivery of a low dose of doxorubicin (DOX). L-Td entered into the cells through endocytosis, and a specific DNA sequence of the L-Td ensures targeted entry into cancer cells. Compared with free DOX, DOX-loaded L-Td (DOX@L-Td) showed decreased clearance and increased initial concentration (C0), half-life, and area under the curve (AUC), indicating that DOX@L-Td circulated in the blood stream for longer than free DOX. L-Td17, in particular, had beneficial effects owing to its ability to enhance tumor accumulation of DOX and reduce the cardiotoxicity caused by it through administration of a low dose of the drug.

Original languageEnglish
Pages (from-to)424-431
Number of pages8
JournalColloids and Surfaces B: Biointerfaces
Volume157
DOIs
StatePublished - 1 Sep 2017

Keywords

  • DNA nanostructure
  • DNA tetrahedron
  • Doxorubicin
  • Live cell imaging
  • Tumor-targeted delivery

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