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

Kyoung Ran Kim, Dohyeon Hwang, Juhyeon Kim, Chang Yong Lee, Wonseok Lee, Dae Sung Yoon, Dongyun Shin, Sun Joon Min, Ick Chan Kwon, Hak Suk Chung, Dae Ro Ahn

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Controlled Release
Volume280
DOIs
Publication statusPublished - 2018 Jun 28

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular and tumor delivery of enzymes'. Together they form a unique fingerprint.

  • Cite this

    Kim, K. R., Hwang, D., Kim, J., Lee, C. Y., Lee, W., Yoon, D. S., Shin, D., Min, S. J., Kwon, I. C., Chung, H. S., & Ahn, D. R. (2018). Streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular and tumor delivery of enzymes. Journal of Controlled Release, 280, 1-10. https://doi.org/10.1016/j.jconrel.2018.04.051