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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. 

Author information

Kim KR1, Kim HY2, Lee YD3, Ha JS2, Kang JH4, Jeong H5, Bang D6, Ko YT4, Kim S7, Lee H8, Ahn DR9.​

1Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Chemistry, College of Science, Yonsei University, Seoul, Republic of Korea.

2Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.

3Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Chemical and Biological Engineering, Korea University, Seoul, Republic of Korea.

4College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Incheon 406-799, Republic of Korea.

5College of Pharmacy, Graduate School of Pharmaceutical Science, Ewha Womans University, Seoul, Republic of Korea.

6Department of Chemistry, College of Science, Yonsei University, Seoul, Republic of Korea.

7Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biological Chemistry, KIST School, Korea University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.

8College of Pharmacy, Graduate School of Pharmaceutical Science, Ewha Womans University, Seoul, Republic of Korea. Electronic address: hyukjin@ewha.ac.kr.

9Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biological Chemistry, KIST School, Korea University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. Electronic address: drahn@kist.re.kr.