Kim, Kyoung-Ran Hwang, Dohyeon Kim, Juhyeon Lee, Chang-Yong Lee, Wonseok Yoon, Dae Sung Shin, Dongyun Min, Sun-Joon Kwon, Ick Chan Chung, Hak Suk Ahn, Dae-Ro 2024-01-19T22:31:45Z 2024-01-19T22:31:45Z 2021-09-03 2018-06-28 0168-3659 https://pubs.kist.re.kr/handle/201004/121235 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. English ELSEVIER SCIENCE BV ARGININE-DEPENDENT CANCERS MAMMALIAN-CELLS L-ASPARAGINASE IN-VITRO PROTEIN THERAPY SYSTEM DRUG NANOPARTICLES DEIMINASE Streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular and tumor delivery of enzymes Article 10.1016/j.jconrel.2018.04.051 1 JOURNAL OF CONTROLLED RELEASE, v.280, pp.1 - 10 JOURNAL OF CONTROLLED RELEASE 280 1 10 scie scopus 000434382100001 2-s2.0-85046513813 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article ARGININE-DEPENDENT CANCERS MAMMALIAN-CELLS L-ASPARAGINASE IN-VITRO PROTEIN THERAPY SYSTEM DRUG NANOPARTICLES DEIMINASE Enzyme delivery Cancer therapy DNA tetrahedron Streptavidin-mirror DNA tetrahedron hybrid