Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age.
Nano Lett
; 23(23): 10971-10982, 2023 Dec 13.
Article
em En
| MEDLINE
| ID: mdl-37991895
ABSTRACT
Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Doença de Alzheimer
Limite:
Animals
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos