4.7 Article

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

期刊

COLLOIDS AND SURFACES B-BIOINTERFACES
卷 157, 期 -, 页码 424-431

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2017.06.014

关键词

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

资金

  1. Basic Science Research Program of the National Research Foundation of Korea [NRF 2017R1A2B4002743]
  2. Pioneer Research Center Program of the National Research Foundation of Korea [NRF 2014M3C1A3054153]
  3. Ministry of Education, Science and Technology
  4. National Research Foundation of Korea [2017R1A2B4002743] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

向作者/读者索取更多资源

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-Td(17)) and the other with 30-mer per side (L-Td(30)) 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 (C-0), half-life, and area under the curve (AUC), indicating that DOX@L-Td circulated in the blood stream for longer than free DOX. L-Td(17), 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. (C) 2017 Elsevier B.V. All rights reserved.

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