期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 21, 页码 8173-8180出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201914751
关键词
antisense oligonucleotides; blood-brain barrier; drug delivery; micelles; self-assembly
资金
- MEXT (JSPS KAKENHI) [25000006, 17H04742]
- Center of Innovation (COI) Program (JST)
- Strategic Research Program for Brain Science (Yuugo Noh, AMED)
- JSPS
- Basic Science and Platform Technology Program for Innovative Biological Medicine (IBIOMED, AMED)
- Grants-in-Aid for Scientific Research [17H04742] Funding Source: KAKEN
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.
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