L-DNA linear duplex: An efficient drug delivery carrier with a simple structure

A-Young Lee; Kyoung-Ran Kim; Jeong Heon Yu; Dae-Ro Ahn

Journal of Industrial and Engineering Chemistry, Vol.74, 187-192, June, 2019

DOI10.1016/j.jiec.2019.02.025 Export Citation

L-DNA linear duplex: An efficient drug delivery carrier with a simple structure

A-Young Lee¹, Kyoung-Ran Kim¹, Jeong Heon Yu¹, and Dae-Ro Ahn^{1, 2, †}

¹The Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea
²Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea

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Three dimensional DNA nanostructures are often limited in scalability due to low assembly yield at high concentrations, leaving themselves less suitable for industrial uses. To overcome this drawback, we here employed L-DNA duplex (L-ds) as a drug carrier. Due to its simple structure, L-ds can easily be prepared at micromolar concentrations without causing any considerable by-product, providing sufficient scalability for practical development. With sufficient cellular uptake efficiency in SCC7 cells and the tumor accumulation level in a SCC7-tumor xenograft mouse model, L-ds could well be utilized as a carrier for intracellular and tumor delivery of an anticancer agent, providing substantial cytotoxicity and inhibition of tumor growth, respectively.

Keywords:L-DNA duplex;Drug delivery;Doxorubicin;Anticancer therapy

[References]

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Williams KP, Liu XH, Schumacher TN, Lin HY, Ausiello DA, Kim PS, Bartel DP, Proc. Natl. Acad. Sci. U. S. A., 94, 11285 (1997)
Kim KR, Lee T, Kim BS, Ahn DR, Chem. Sci., 5, 1533 (2014)
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Matsumura Y, Maeda H, Cancer Res., 46, 6387 (1986)

[1] stank G, Cerny M, Kocourek J, Pacak J, The Monosaccharides, Academic Press, New York, pp77 1973.

[2] Anderson DJ, Reischer RJ, Taylor AJ, Wechter WJ, Nucleosides Nucleotides Nucleic Acids, 3, 499 (1984)

[3] Reese CB, Tetrahedron, 34, 3143 (1978)

[4] Narang S, Brousseau R, Hsiung H, Michniewicz J, Methods Enzymol., 65, 610 (1980)

[5] Urata H, Shinohara K, Ogura E, Ueda Y, Akagi M, J. Am. Chem. Soc., 113, 8174 (1991)

[6] Fujimori S, Shudo K, Hashimoto Y, J. Am. Chem. Soc., 112, 7436 (1990)

[7] Kim Y, Yang CJ, Tan W, Nucleic Acids Res., 35, 7279 (2007)

[8] Hauser NC, Martinez R, Jacob A, Rupp S, Hoheisel JD, Matysiak S, Nucleic Acids Res., 34, 5101 (2006)

[9] Urata H, Ogura E, Shinohara K, Ueda Y, Akagi M, Nucleic Acids Res., 20, 3325 (1992)

[10] Ke GL, Wang CM, Ge Y, Zheng NF, Zhu Z, Yang CJ, J. Am. Chem. Soc., 134(46), 18908 (2012)

[11] Williams KP, Liu XH, Schumacher TN, Lin HY, Ausiello DA, Kim PS, Bartel DP, Proc. Natl. Acad. Sci. U. S. A., 94, 11285 (1997)

[12] Kim KR, Lee T, Kim BS, Ahn DR, Chem. Sci., 5, 1533 (2014)

[13] Kim KR, Kim HY, Lee YD, Ha JS, Kang JH, Jeong H, Bang D, Ko YT, Kim S, Lee H, Ahn DR, J. Control. Release, 243, 121 (2016)

[14] Kim KR, Kim DR, Lee T, Yhee JY, Kim BS, Kwon IC, Ahn DR, Chem. Commun., 49, 2010 (2013)

[15] Kim KR, Kang SJ, Lee AY, Hwang D, Park M, Park H, Kim S, Hur K, Chung HS, Mao C, Ahn DR, Biomaterials, 195, 1 (2019)

[16] Matsumura Y, Maeda H, Cancer Res., 46, 6387 (1986)