Self-assembled mirror DNA nanostructures for tumor-specific delivery of anticancer drugs

Kyoung Ran Kim, Hyo Young Kim, Yong Deok Lee, Jong Seong Ha, Ji Hee Kang, Hansaem Jeong, Duhee Bang, Young Tag Ko, Sehoon Kim, Hyukjin Lee, Dae Ro Ahn

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

Nanoparticle delivery systems have been extensively investigated for targeted delivery of anticancer drugs over the past decades. However, it is still a great challenge to overcome the drawbacks of conventional nanoparticle systems such as liposomes and micelles. Various novel nanomaterials consist of natural polymers are proposed to enhance the therapeutic efficacy of anticancer drugs. Among them, deoxyribonucleic acid (DNA) has received much attention as an emerging material for preparation of self-assembled nanostructures with precise control of size and shape for tailored uses. In this study, self-assembled mirror DNA tetrahedron nanostructures is developed for tumor-specific delivery of anticancer drugs. L-DNA, a mirror form of natural D-DNA, is utilized for resolving a poor serum stability of natural D-DNA. The mirror DNA nanostructures show identical thermodynamic properties to that of natural D-DNA, while possessing far enhanced serum stability. This unique characteristic results in a significant effect on the pharmacokinetics and biodistribution of DNA nanostructures. It is demonstrated that the mirror DNA nanostructures can deliver anticancer drugs selectively to tumors with enhanced cellular and tissue penetration. Furthermore, the mirror DNA nanostructures show greater anticancer effects as compared to that of conventional PEGylated liposomes. Our new approach provides an alternative strategy for tumor-specific delivery of anticancer drugs and highlights the promising potential of the mirror DNA nanostructures as a novel drug delivery platform.

Original languageEnglish
Pages (from-to)121-131
Number of pages11
JournalJournal of Controlled Release
Volume243
DOIs
Publication statusPublished - 2016 Dec 10
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by Global Innovative Research Center program ( 2012K1A1A2A01055811 ) of the National Research Foundation of Korea and by the Intramural Research Programs (Global RNAi Carrier Initiative and Convergence Technology Program) of KIST, the National Research Foundation of Korea (NRF) grant funded by the Korea government ( MSIP ) ( 2014-R1A2A2A04002526 ), and a grant by the Pioneer Research Center Program through NRF funded by the Ministry of Science, ICT and Future Planning ( 2014M3C1A3054141 ).

Keywords

  • DNA nanostructure
  • Doxorubicin
  • Mirror DNA
  • Tumor-targeted delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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