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Systemic Brain Delivery of Antisense Oligonucleotides across the Blood-Brain Barrier with a Glucose-Coated Polymeric Nanocarrier.


ABSTRACT: 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.

SUBMITTER: Min HS 

PROVIDER: S-EPMC7317551 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Systemic Brain Delivery of Antisense Oligonucleotides across the Blood-Brain Barrier with a Glucose-Coated Polymeric Nanocarrier.

Min Hyun Su HS   Kim Hyun Jin HJ   Naito Mitsuru M   Ogura Satomi S   Toh Kazuko K   Hayashi Kotaro K   Kim Beob Soo BS   Fukushima Shigeto S   Anraku Yasutaka Y   Miyata Kanjiro K   Kataoka Kazunori K  

Angewandte Chemie (International ed. in English) 20200306 21


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  ...[more]

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