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J Control Release. 2018 Jun 28;280:1-10. doi: 10.1016/j.jconrel.2018.04.051. Epub 2018 Apr 30.

Streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular and tumor delivery of enzymes.

Author information

1
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
2
Center for Neuro-Medicine, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
3
College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Incheon 21936, Republic of Korea.
4
Department of Biomedical Engineering, Yonsei University, Wonju 26493, Republic of Korea.
5
School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea.
6
Department of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of Korea.
7
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Division of Biomedical Science and Technology, Korea University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
8
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Division of Biomedical Science and Technology, Korea University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea. Electronic address: drahn@kist.re.kr.

Abstract

Despite the extremely high substrate specificity and catalytically amplified activity of enzymes, the lack of efficient cellular internalization limits their application as therapeutics. To overcome this limitation and to harness enzymes as practical biologics for targeting intracellular functions, we developed the streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular delivery of various enzymes. The hybrid consists of streptavidin, which provides a stoichiometrically controlled loading site for the enzyme cargo and an L-DNA (mirror DNA) tetrahedron, which provides the intracellular delivery potential. Due to the cell-penetrating ability of the mirror DNA tetrahedron of this hybrid, enzymes loaded on streptavidin can be efficiently delivered into the cells, intracellularly expressing their activity. In addition, we demonstrate tumor delivery of enzymes in an animal model by utilizing the potential of the hybrid to accumulate in tumors. Strikingly, the hybrid is able to transfer the apoptotic enzyme specifically into tumor cells, leading to strong suppression of tumor growth without causing significant damage to other tissues. These results suggest that the hybrid may allow anti-proliferative enzymes and proteins to be utilized as anticancer drugs.

KEYWORDS:

Cancer therapy; DNA tetrahedron; Enzyme delivery; Streptavidin-mirror DNA tetrahedron hybrid

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