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

38 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

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program (NRF 2017R1A2B4002743) and the Pioneer Research Center Program (NRF 2014M3C1A3054153) of the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology.

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

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

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