Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age

Gregory C. Tracy, Kai Yu Huang, Yu Tong Hong, Shengzhe Ding, Hayden A. Noblet, Ki H. Lim, Eung Chang Kim, Hee Jung Chung, Hyunjoon Kong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)10971-10982
Number of pages12
JournalNano letters
Volume23
Issue number23
DOIs
StatePublished - Dec 13 2023

Keywords

  • aging
  • Alzheimer’s disease
  • blood-brain barrier
  • hyaluronic acid
  • PLGA nanoparticles
  • reactive astrocytes

ASJC Scopus subject areas

  • Bioengineering
  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanical Engineering

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