고영탁 (가천대학교 약학대학)

한빛사논문

조회69

가천대학교 약학대학

Small Methods, Aug 02 2024, | https://doi.org/10.1002/smtd.202400902 Systemic Brain Delivery of Oligonucleotide Therapeutics Enhanced by Protein Corona-Assisted DNA Cubes

Kyoung-Ran Kim ¹, Ji Hee Kang², Hien Bao Dieu Thai ¹, Ji Hyun Back ¹, Chengde Mao ³, Ji Eun Lee¹, Young Tag Ko ², Dae-Ro Ahn ^1,4

¹Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea.

²College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Incheon, 21936, Republic of Korea.

³Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.

⁴Division of Biomedical Science and Technology, KIST School, Korea National University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea.

K.-R.K. and J.H.K. contributed equally to this work.

Corresponding Authors: Young Tag Ko, Dae-Ro Ahn

Abstract

The systemic delivery of oligonucleotide therapeutics to the brain is challenging but highly desirable for the treatment of brain diseases undruggable with traditional small-molecule drugs. In this study, a set of DNA nanostructures is prepared and screened them to develop a protein corona-assisted platform for the brain delivery of oligonucleotide therapeutics. The biodistribution analysis of intravenously injected DNA nanostructures reveals that a cube-shaped DNA nanostructure (D-Cb) can penetrate the brain-blood barrier (BBB) and reach the brain tissue. The brain distribution level of D-Cb is comparable to that of other previous nanoparticles conjugated with brain-targeting ligands. Proteomic analysis of the protein corona formed on D-Cb suggests that its brain distribution is driven by endothelial receptor-targeting ligands in the protein corona, which mediate transcytosis for crossing the BBB. D-Cb is subsequently used to deliver an antisense oligonucleotide (ASO) to treat glioblastoma multiforme (GBM) in mice. While free ASO is unable to reach the brain, ASO loaded onto D-Cb is delivered efficiently to the brain tumor region, where it downregulates the target gene and exerts an anti-tumor effect on GBM. D-Cb is expected to serve as a viable platform based on protein corona formation for systemic brain delivery of oligonucleotide therapeutics.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-05)
연구진국내 연구진
분야 의약학 > 약학

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