Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32431145.
- Also identified by DOI 10.1021/acsnano.9b09991.
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Abstract
Delivering therapeutic antibodies into the brain across the blood-brain barrier at a therapeutic level is a promising while challenging approach in the treatment of neurological disorders. Here, we present a polymeric nanomicelle (PM) system capable of delivering therapeutically effective levels of 3D6 antibody fragments (3D6-Fab) into the brain parenchyma for inhibiting Aβ aggregation. PM assembly was achieved by charge-converting 3D6-Fab through pH-sensitive citraconylation to allow complexation with reductive-sensitive cationic polymers. Brain targeting was achieved by functionalizing the PM surface with glucose molecules to allow interaction with recycling glucose transporter (Glut)-1 proteins. Consequently, 41-fold enhanced 3D6-Fab accumulation in the brain was achieved by using the PM system compared to free 3D6-Fab. Furthermore, therapeutic benefits were obtained by successfully inhibiting Aβ<sub>1-42</sub> aggregation in Alzheimer's disease mice systemically treated with 3D6-Fab-loaded glucosylated PM. Hence, this nanocarrier system represents a promising method for effectively delivering functional antibody agents into the brain and treating neurological diseases.
Medical subject headings
- Alzheimer Disease
- Amyloid beta-Peptides