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Systemic Brain Delivery of Antisense Oligonucleotides across the Blood–Brain Barrier with a Glucose‐Coated Polymeric Nanocarrier
Author(s) -
Min Hyun Su,
Kim Hyun Jin,
Naito Mitsuru,
Ogura Satomi,
Toh Kazuko,
Hayashi Kotaro,
Kim Beob Soo,
Fukushima Shigeto,
Anraku Yasutaka,
Miyata Kanjiro,
Kataoka Kazunori
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201914751
Subject(s) - nanocarriers , blood–brain barrier , systemic administration , oligonucleotide , gene knockdown , central nervous system , chemistry , pharmacology , medicine , nanotechnology , drug delivery , biophysics , materials science , dna , biology , biochemistry , in vivo , gene , microbiology and biotechnology
Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders.